Intravenous Gonadotropin-releasing Hormone Research Articles

The utilization of basal luteinizing hormone in combination with the basal luteinizing hormone and follicle-stimulating hormone ratio as a diagnostic tool for central precocious puberty in girls.

Intravenous gonadotropin-releasing hormone (IV GnRH) testing is the gold standard for confirming a central precocious puberty (CPP) diagnosis. However, this test is not widely available commercially. Therefore, our study aim was to establish cutoff values for basal gonadotropin level and gonadotrophin responses to a 100-μg subcutaneous IV GnRH test that can distinguish between CPP and premature thelarche (PT) to discover a simple method to detect CPP. Girls between the ages of 6 and 8 years who attended the pediatric endocrinology outpatient clinic at our tertiary hospital between 2019 and 2022 were included in this study. They were evaluated for breast development, and a subcutaneous 100-μg GnRH test was administered by measuring the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in blood samples at baseline and then 30, 60, 90, and 120 minutes after injection. CPP is characterized by increased height velocity, advanced bone age, and progression of breast development. The cutoff value for diagnosis of CPP was determined using a receiver operating characteristic (ROC) analysis. In 86 Thai girls (56 with CPP and 30 with PT), the ROC analysis showed 71.4% and 100% sensitivity and specificity, respectively, for basal LH (cutoff ≥ 0.2 IU/L) plus the basal LH/FSH ratio (cutoff ≥ 0.1). The optimal cutoff values for peak LH (cutoff ≥ 7 IU/L) demonstrated a sensitivity of 94.6% and a specificity of 100%, whereas the LH value at 30 and 60 minutes after injection (cutoff ≥ 6 IU/L) demonstrated sensitivities of 92.9% and 94.6% and a specificity of 100%, respectively. Combining the basal LH (cutoff: 0.2 IU/L) and the basal LH/FSH ratio (cutoff: 0.1) can easily and cost-effectively diagnose CPP in a girl in breast Tanner stage II.

Impact of 6-month triptorelin formulation on predicted adult height and basal gonadotropin levels in patients with central precocious puberty.

Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables. We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently. The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment. The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected.

702 CLINICAL FEATURES AND TESTICULAR MORPHOLOGY IN INFANTILE PATIENTS WITH KALLMANN SYNDROME

You have accessJournal of UrologyPenis/Testis/Urethra: Benign & Malignant Disaese (I)1 Apr 2013702 CLINICAL FEATURES AND TESTICULAR MORPHOLOGY IN INFANTILE PATIENTS WITH KALLMANN SYNDROME Hidenori Nishio, Kentaro Mizuno, Satoshi Kurokawa, Hideyuki Kamisawa, Makoto Imura, Yoshinobu Moritoki, Yasuhiro Shibata, Akihiro Nakane, Toshiki Kato, Tetsuji Maruyama, Yoshiyuki Kojima, Yutaro Hayashi, and Kenjiro Kohri Hidenori NishioHidenori Nishio Nagoya, Japan More articles by this author , Kentaro MizunoKentaro Mizuno Nagoya, Japan More articles by this author , Satoshi KurokawaSatoshi Kurokawa Nagoya, Japan More articles by this author , Hideyuki KamisawaHideyuki Kamisawa Nagoya, Japan More articles by this author , Makoto ImuraMakoto Imura Nagoya, Japan More articles by this author , Yoshinobu MoritokiYoshinobu Moritoki Nagoya, Japan More articles by this author , Yasuhiro ShibataYasuhiro Shibata Nagoya, Japan More articles by this author , Akihiro NakaneAkihiro Nakane Nagoya, Japan More articles by this author , Toshiki KatoToshiki Kato Nagoya, Japan More articles by this author , Tetsuji MaruyamaTetsuji Maruyama Nagoya, Japan More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima Nagoya, Japan More articles by this author , Yutaro HayashiYutaro Hayashi Nagoya, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.260AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Kallmann syndrome (KS) is a genetic disorder characterized by the simultaneous occurrence of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia. Although there have been some reports about genes responsible for KS, their impact on the testicular tissue of KS during infantile periods remains unclear. We retrospectively reviewed the patients clinically diagnosed KS, and evaluated the testicular morphology of KS these patients by performing testicular biopsies during orchiopexy. METHODS A retrospective assessment was conducted of 4 cryptorchid patients diagnosed with KS. The assessment included a determination of the chief complaints of the patients upon presentation, the age at which the orchiopexy was performed, and the results of hormone tests, including tests for luteinizing hormone-releasing hormone and human chorionic gonadotropin (hCG). In addition, testicular morphology was assessed during testicular biopsy, and histrogical examinations were performed. Especially the presence of Leydig cells was examined by immunohistochemistry using antibodies against Ad4BP/SF1. RESULTS Laboratory testing showed low values of LH, FSH, and testosterone, confirming hypogonadotropic hypogonadism. LH and FSH did not increase in response to intravenous gonadotropin-releasing hormone treatment; hCG tests also failed to show changes in testosterone levels. Head magnetic resonance imaging scans failed to show evidence of pituitary tumors but showed deficiencies in the olfactory bulbs and grooves. Histologic examinations of the testes showed immature seminiferous tubules with mild interstitial fibrosis and edema; spermatogonia were not detected. Leydig cells were detectable in the testis of the interstitium and Sertoli cells in the seminiferous tubules by immunohistochemistry using antibodies against Ad4BP/SF1 in the testes of one patient. CONCLUSIONS Although the diagnosis of KS before puberty is difficult, LH-RH and hCG tests were useful for the differential diagnosis. The present study showed the presence of Leydig cells in the testis of one patient with IHH using immunohistochemistry for Ad4BP/SF1, even though Leydig cells were reportedly absent. Testicular morphology in the patients with KS is more varied than expected, and further investigations are required to elucidate the hormonal effects on normal testicular development. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e289 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidenori Nishio Nagoya, Japan More articles by this author Kentaro Mizuno Nagoya, Japan More articles by this author Satoshi Kurokawa Nagoya, Japan More articles by this author Hideyuki Kamisawa Nagoya, Japan More articles by this author Makoto Imura Nagoya, Japan More articles by this author Yoshinobu Moritoki Nagoya, Japan More articles by this author Yasuhiro Shibata Nagoya, Japan More articles by this author Akihiro Nakane Nagoya, Japan More articles by this author Toshiki Kato Nagoya, Japan More articles by this author Tetsuji Maruyama Nagoya, Japan More articles by this author Yoshiyuki Kojima Nagoya, Japan More articles by this author Yutaro Hayashi Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

A novel animal model to study hot flashes

Menopausal hot flashes compromise the quality of life for most women. The physiological mechanisms underlying hot flashes remain poorly understood, and the absence of an animal model to investigate hot flashes hinders investigations in this field. We first developed the sheep as a model to study peripheral skin temperature changes using fever-inducing lipopolysaccharide (LPS; 200 microg/kg) administered to ovary-intact ewes. Because a strong correlation between luteinizing hormone pulses and hot flashes has previously been reported, we then determined whether intravenous gonadotropin-releasing hormone (GnRH; 1 mg), a dose sufficient to elevate cerebrospinal fluid-GnRH concentrations, could modulate ear skin temperature in both ovariectomized and low-estrogen-replaced ovariectomized ewes. Some ewes responded to LPS in heart rate and abdominal temperature, but there was no significant effect on either parameter or cheek temperature for the group. In contrast, LPS injection caused a significant (P < 0.001) change in skin temperature at the ear. Ear temperature showed no significant change in response to GnRH relative to control injections in both ovariectomized and low estrogen ewes. We developed a model animal system in the ewe that can accurately detect small changes in peripheral skin temperature. This system has the potential to be extremely useful in future studies investigating the pathology of hot flashes and holds several advantages over previous model systems developed for this research. GnRH per se does not seem to be involved in thermoregulatory events.

Subcutaneous Gonadotropin-Releasing Hormone Agonist (Triptorelin) Test for Diagnosing Precocious Puberty

Background: A test involving 100 μg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. Objective: To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. Methods: A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 μg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Results: Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93–65.39) and 3.04 IU/l (0.19–8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Conclusion: Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP.

Analysis of gonadotropin-releasing hormone (GnRH) test results in girls with precocious puberty

Purpose : The gonadotropin-releasing hormone (GnRH) test results of girls with precocious puberty were analyzed to determine whether this test can efficiently and clearly differentiate between central precocious puberty (CPP) and other disorders. Methods : Clinical and laboratory data of 54 girls with precocious pubertal signs were reviewed. Intravenous GnRH test was performed with blood samples obtained at 0, 30, 60, and 90 minutes. A peak luteinizing hormone (LH) level of ≥5.0 IU/L was indicative of CPP. Results : Of the 40 girls with CPP, 36 (90.0%), 3 (7.5%), and 1 (2.5%) showed peak LH levels at 30, 60, and 90 minutes, respectively. A percentage of girls whose peak LH ≥5.0 IU/L up to 30, 60, and 90 minutes was 92.5%, 100%, and 100%, respectively. The peak LH/follicle stimulating hormone (FSH) ratio of girls with CPP was 0.89±0.49 and was 1.0 showed higher chronological age (CA) (8.3±0.6 vs. 7.7±1.0 years, P=0.033), bone age (BA) (10.9±0.8 vs. 9.7±1.1 years, P=0.001), and BA-CA difference (2.6±0.7 vs. 2.0±0.7 years, P=0.009) than those of girls with peak LH/FSH ratio of ≤1.0. Higher percentage of girls with peak LH/FSH ratio of >1.0 showed advanced breast development (≥Tanner III) (93.7% vs. 41.7%, P=0.001). Conclusion : LH levels after 30 and 60 minutes of intravenous GnRH administration are the most useful for diagnosing CPP in girls. (Korean J Pediatr 2009;52:1377-1382)

Effects of a gonadotropin-releasing hormone antagonist and altrenogest on luteinizing hormone concentration and ovulation in the mare

The objective of Experiment 1 was to determine a dose and frequency of gonadotropin-releasing hormone (GnRH) antagonist administration to effectively suppress serum luteinizing hormone (LH) concentration and to delay ovulation when administered to mares. The objectives of Experiment 2 were 1) to determine the effects of subcutaneous or intravenous administration of a GnRH antagonist or oral altrenogest on serum LH concentration in the estrual mare; and 2) to determine the effectiveness of human chorionic gonadotropin (hCG) in inducing ovulation in mares with suppressed LH concentrations. In Experiment 1, mares ( N = 20) were randomly assigned and treated with either 5% mannitol (control, single subcutaneous injection, 1 mL, at time 0; n = 5); low-dose GnRH antagonist (single subcutaneous injection, 0.01 mg/kg, at time 0; n = 5); frequent low-dose GnRH antagonist (subcutaneous injections, 0.01 mg/kg, at 0, 6, 18, and 24 hours; n = 5); or high-dose GnRH antagonist (single subcutaneous injection, 0.04 mg/kg, at time 0; n = 5). Both the frequent low-dose and high-dose GnRH antagonist treatments resulted in significantly lower LH concentrations compared with controls at 90, 102, and 114 hours after treatment ( P < .05). In Experiment 2, mares (N = 38) were randomly assigned and treated with subcutaneous sterile saline (control), altrenogest (oral), subcutaneous GnRH antagonist, or intravenous GnRH antagonist. LH concentration for the altrenogest group was lower than the control group at 3, 4, 18, and 30 hours after treatment ( P < .05). LH concentration for both the subcutaneous and intravenous GnRH antagonist groups were lower compared with the control group at several time points ( P < .05). Based on these data, dose but not frequency of administration of a GnRH antagonist lowered LH concentration in the estrous mare but did not delay ovulation. In addition, serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG. This indicates that serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG.

Effects of a GnRH antagonist inhibition of luteinizing hormone during the preovulatory period in the mare

The objective of Experiment 1 was to determine a dose and frequency of gonadotropin-releasing hormone (GnRH) antagonist administration to effectively suppress serum luteinizing hormone (LH) concentration and to delay ovulation when administered to mares. The objectives of Experiment 2 were 1) to determine the effects of subcutaneous or intravenous administration of a GnRH antagonist or oral altrenogest on serum LH concentration in the estrual mare; and 2) to determine the effectiveness of human chorionic gonadotropin (hCG) in inducing ovulation in mares with suppressed LH concentrations. In Experiment 1, mares (N = 20) were randomly assigned and treated with either 5% mannitol (control, single subcutaneous injection, 1 mL, at time 0; n = 5); low-dose GnRH antagonist (single subcutaneous injection, 0.01 mg/kg, at time 0; n = 5); frequent low-dose GnRH antagonist (subcutaneous injections, 0.01 mg/kg, at 0, 6, 18, and 24 hours; n = 5); or high-dose GnRH antagonist (single subcutaneous injection, 0.04 mg/kg, at time 0; n = 5). Both the frequent low-dose and high-dose GnRH antagonist treatments resulted in significantly lower LH concentrations compared with controls at 90, 102, and 114 hours after treatment (P < .05). In Experiment 2, mares (N = 38) were randomly assigned and treated with subcutaneous sterile saline (control), altrenogest (oral), subcutaneous GnRH antagonist, or intravenous GnRH antagonist. LH concentration for the altrenogest group was lower than the control group at 3, 4, 18, and 30 hours after treatment (P < .05). LH concentration for both the subcutaneous and intravenous GnRH antagonist groups were lower compared with the control group at several time points (P < .05). Based on these data, dose but not frequency of administration of a GnRH antagonist lowered LH concentration in the estrous mare but did not delay ovulation. In addition, serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG. This indicates that serum LH concentrations can be lowered and ovulation effectively postponed in mares treated with altrenogest followed by administration of hCG.

A randomized controlled study comparing the endocrine effects of pulsatile intravenous gonadotropin-releasing hormone after gonadotropin-releasing hormone agonist pretreatment versus clomiphene citrate in patients with polycystic ovary syndrome

Objective: To compare the endocrine changes in the follicular phase in infertile patients with polycystic ovary syndrome (PCOS) treated with either pulsatile IV GnRH after GnRH-agonist (GnRH-a) down-regulation or clomiphene citrate (CC). Design: Subgroup analysis within a randomized, controlled, multicenter study. Setting: Women referred to the Infertility Clinic, Catharina Hospital Eindhoven, The Netherlands. Patient(s): Twenty-eight infertile patients with PCOS. Intervention(s): Patients were randomly assigned to pulsatile IV GnRH (10–20 μg/90 min) after GnRH-a down-regulation or CC (50–150 mg; cycle days 3–7). Patients were monitored on alternate days with ovarian sonography and serum concentrations of E 2, LH, and FSH. Serum P and sonography confirmed ovulation. Main Outcome Measure(s): Serum concentrations of E 2, LH, and FSH were assessed before treatment was started and after each ovarian sonography. Result(s): In ovulatory cycles, no statistically significant differences were observed during the follicular phase comparing serum concentrations of E 2, LH, and FSH between the treatments. However, a significant increase in LH occurred in the GnRH group. Conclusion(s): No significant endocrine differences were observed between GnRH and CC treatment. However, there was a significant increase in the serum LH concentration during the follicular phase in the GnRH group. Increments of LH in the GnRH group may be due to recovery of endogenous LH secretion.

The effects of exogenous growth hormone on follicular steroid secretion and ovulation rate in sheep

Growth hormone (GH) has diverse actions in many tissues, including the follicle. This paper summarizes three experiments that examined the effects of GH and insulin-like growth factor (IGF)-I on the ovary. Ewes given oGH and pregnant mane serum gonadotrophin were compared with control and pregnant mane serum gonadotrophin-treated ewes. Ewes, with synchronized cycles, were given varying doses of pregnant mane serum gonadotrophin and/or oGH to determine if oGH is able to augment ovulation rate (Experiment 1). Experiments 2 and 3 used the ovarian autotransplant model. Ewes were infused via the ovarian artery with oGH (Experiment 2) or insulin-like growth factor I (IGF-I) (Experiment 3). Both were administered for 12 hr on Day 10. In Experiment 2, ewes were given intravenous gonadotropin releasing hormone (150 ng iv) at −2.5 and 10.5 hr relative to infusion. Ovarian and jugular venous blood was collected every 15 min from −30 to 150 min relative to gonadotropin releasing hormone. In Experiment 3, luteolysis was induced at the end of infusion. Ovarian and jugular venous blood was collected every 3 hr from before and until 84 hr after the infusion. Estradiol and androstenedione were assayed in ovarian venous plasma and GH in jugular venous plasma. In Experiment 1, treatment with oGH increased the jugular venous concentration of GH. However, in Experiment 2 treatment with oGH via the ovarian artery did not increase jugular venous GH but did increase ovarian venous GH. Treatment with oGH had no effect on ovulation rate (Experiment 1) or the secretion of androstenedione and estradiol (Experiment 2). Infusion of IGF-I (Experiment 3) increased the secretion of estradiol during the follicular phase. These data show that short-term treatment of sheep with GH had no in vivo effects on the follicle and that IGF-I was a potent stimulator of follicular steroidogenesis in vivo.

The effects of etoposide on testicular function in boys treated for Hodgkin's disease.

Testicular dysfunction with elevated follicle-stimulating hormone (FSH) levels (indicating oligospermia and/or azoospermia) is a major late sequelae after treatment for Hodgkin's disease (HD) with high cumulative doses of procarbazine, cyclophosphamide, or chlorambucil. Etoposide is a newer antineoplastic agent that is effective in the treatment of HD. However, little is known regarding its testicular toxicity, especially in the pediatric age group. The authors evaluated testicular function in 46 young adults in first continuous complete remission after stage-dependent treatment for HD with the vincristine, etoposide, prednisone, and doxorubicin (OEPA) or OEPA/cyclophosphamide, vincristine, procarbazine, and prednisone [COPP] chemotherapy regimens and involved field irradiation, excluding patients with ilioinguinal radiotherapy. Pubertal development was documented and a standardized intravenous gonadotropin-releasing hormone test was performed measuring testosterone and basal and stimulated levels of FSH and luteinizing hormone (LH). Testicular volumes, Tanner stages of pubic hair, and genital development were found to be appropriate or slightly delayed for the patients' chronologic age. All 27 patients had normal basal levels of FSH and LH after treatment of Ann Arbor Stage I-IIA HD with 2 courses of OEPA. Stimulated FSH and LH levels were found to be elevated only in rare patients, thus indicating normal endocrine function and spermatogenesis. However, basal and stimulated FSH levels were outside the +2 standard deviation range in 37.5% and 83.3% of patients receiving 2 cycles of OEPA and 2 cycles of COPP chemotherapy, and in 36.4% and 66.7% of patients receiving 2 cycles of OEPA and 4 cycles of COPP chemotherapy, demonstrating a high risk of oligospermia or azoospermia with these regimens. Basal LH levels essentially were normal, whereas stimulated LH levels frequently were elevated. Testicular function was found to be normal in patients with Stage I-IIA HD when etoposide was used in combination with vincristine, prednisone, and doxorubicin (2 cycles of OEPA). Additional chemotherapy with cyclophosphamide and procarbazine (2 cycles of OEPA and 2 or 4 cycles of COPP) negatively affected spermatogenesis and possibly Leydig cell function in a considerable number of patients. This major gonadotoxic effect most likely is due to procarbazine, although an additional effect of etoposide and cyclophosphamide cannot be excluded.

Is GnRH Reduced at the Midcycle Surge in the Human?

Recent studies indicate that the midcycle gonadotropin surge in the human occurs without an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency. In addition, previous studies employing a GnRH antagonist to provide a semiquantitative estimate of endogenous GnRH secretion suggest that the overall amount of GnRH secreted is decreased at the time of the surge. To investigate the hypothesis that a normal gonadotropin surge can be generated in the human with a decreased amount of GnRH at the midcycle, 7 GnRH-deficient subjects underwent two cycles of a physiologic regimen of intravenous pulsatile GnRH therapy. In the control cycle, 75 ng/kg/bolus of GnRH, a dose known to be sufficient for folliculogenesis, was administered throughout the cycle, using physiological frequencies. In a second cycle, the bolus dose of GnRH was decreased by one-half log order to 25 ng/kg just prior to the luteinizing hormone surge and returned to 75 ng/kg after documented ovulation. All cycles were ovulatory. The peak luteinizing hormone level (77.4±9.7 vs. 67.5±17.6 IU/l) did not differ between the control and decreased GnRH cycles. There was no difference in the peak serum estradiol level (475.8±144.1 vs. 493.2±93.0 pg/ml), follicular phase length (15.0±1.3 vs. 14.8±0.6 days), or progesterone level (22.4±5.1 vs. 34.8±5.7 ng/ml) on day 6 of the luteal phase in the control and decreased GnRH cycles, respectively. Three pregnancies were achieved in each of the control and reduced GnRH cycles. We conclude that a decreased overall amount of GnRH generates a normal midcycle gonadotropin surge and has no significant impact on luteal phase adequacy or fertility. These results provide further evidence that a decrease in endogenous hypothalamic GnRH secretion may occur at the midcycle in normal women. This study also provides evidence that the GnRH requirements for normal follicular and luteal phase dynamics may well be greater than those required for generation of a normal midcycle gonadotropin surge and ovulation in women.

Differential dynamic responses of luteinizing hormone to gonadotropin releasing hormone in patients affected by bulimia nervosa-purging versus non-purging type.

Aim of the study was to investigate the presence of underlying abnormalities affecting the hypothalamus-pituitary-gonadal axis in 13 normal weight eumenhorreic bulimics as expressed by a different gonadotropin response to gonadotropin releasing hormone (GnRH), comparing patients with (n = 6) and without (n = 7) purging behaviours to controls (n = 5). Subjects were administered an intravenous GnRH infusion for four hours, with an additional bolus at first and third hour. Non-purging bulimics showed a significantly reduced luteinizing hormone (LH) response to GnRH compared to controls; purging bulimics, following the second bolus, demonstrated a statistically reduced peak, in comparison to both controls and non-purging bulimics. even in the absence of overt menstrual disturbances, an altered LH secretion elicited by pulsatile stimulation of endogenous GnRH was found, with a more severe impairment in purging than in non-purging bulimics, possibly related to their greater psychopathological and physical burden.

Pulsatile Intravenous Gonadotropin-Releasing Hormone Administration Averts Fasting-Induced Hypogonadotropism and Hypoandrogenemia in Healthy, Normal Weight Men

Pulsatile Intravenous Gonadotropin-Releasing Hormone Administration Averts Fasting-Induced Hypogonadotropism and Hypoandrogenemia in Healthy, Normal Weight Men

Pulsatile intravenous gonadotropin-releasing hormone administration averts fasting-induced hypogonadotropism and hypoandrogenemia in healthy, normal weight men.

Fasting or severe caloric restriction in the human or experimental animal suppresses serum LH and sex steroid concentrations. In healthy men undergoing prolonged (5-day) nutrient deprivation, the daily LH secretion rate, the mass of LH secreted per burst, and the serum testosterone concentration fall markedly, with no decrease in responsiveness to a single bolus of GnRH. Here we test the hypothesis that the hypogonadotropic hypoandrogenemia accompanying fasting reflects decreased endogenous GnRH release. To this end, six healthy young men were studied on a fed day and during two 83-h fasting sessions with concurrent saline or pulsatile GnRH administration (100 ng/kg, i.v., every 90 min for 24 h) followed by a single bolus of 10 microg GnRH, i.v., to evaluate pituitary responsiveness. We employed a highly sensitive LH immunoradiometric assay, which correlates well with an in vitro Leydig cell bioassay, and deconvolution analysis to calculate in vivo LH secretory burst frequency, amplitude, duration, mass, and LH half-life. Fasting resulted in 30-50% declines in serum total and free testosterone and LH concentrations, and a 3-fold decrease in the calculated 24-h LH secretion rate (fed, 42 +/- 12; fasting, 14 +/- 1.9 U/L distribution volume x day; mean +/- SEM; P < 0.05, by ANOVA). Reduced LH secretion was accounted for by dual mechanisms, viz. a fall in both the apparent number of computer-resolved LH secretory bursts per 24 h (fed, 16 +/- 1.1; fasting, 10 +/- 1.2; P < 0.01) and the mass of LH secreted per burst (fed, 2.5 +/- 0.5; fasting, 1.5 +/- 0.1 U/L; P < 0.05). Fasting also decreased the mean value of the 24-h (nyctohemeral) rhythm in serum LH concentrations and reduced the approximate entropy (disorderliness) of LH release. Exogenous pulsatile GnRH injections prevented both the reduction in the calculated daily LH secretion rate (fed, 42 +/- 12; fasting plus GnRH, 64 +/- 16 IU/L; P = NS) and the decline in serum testosterone concentrations (fed, 556 +/- 71 ng/dL; fasting, 391 +/- 41; fasting plus GnRH, 859 +/- 65). Pulsatile GnRH treatment also restored the nyctohemeral mesor of serum LH concentrations and the approximate entropy value to baseline. Administration of a submaximal dose of exogenous GnRH (10 microg, i.v.) at the end of the fasting interval revealed statistically identical LH release in the three study groups, suggesting that pituitary responsiveness to GnRH was unchanged in this paradigm. In summary, a pulsatile iv GnRH infusion in young men averts completely the fasting-induced decline in LH secretory burst mass/amplitude and frequency, reinstates serum total and free testosterone concentrations, and restores the mesor of LH's nyctohemeral rhythmicity and the approximate entropy of LH release. Rescue of hypogonadism by pulsatile GnRH stimuli supports the thesis that nutrient withdrawal decreases the output of the human hypothalamic GnRH burst generator.

O-121 A randomized controlled study comparing endocrine effects of pulsatile intravenous gonadotropin releasing hormone (GnRH) after GnRH-agonist pretreatment and clomiphene citrate (CC) in polycystic ovary syndrome (PCOS)-patients

O-121 A randomized controlled study comparing endocrine effects of pulsatile intravenous gonadotropin releasing hormone (GnRH) after GnRH-agonist pretreatment and clomiphene citrate (CC) in polycystic ovary syndrome (PCOS)-patients

Basal and stimulated gonadotropin levels in the perimenopause

OBJECTIVE: We investigated whether perimenopausal menstrual cycle irregularity is associated with increased gonadotropin immunoactivity, bioactivity, or the bioactivity/immunoactivity ratio at baseline and after short-term stimulation with gonadotropin-releasing hormone. STUDY DESIGN: Subjects consisted of four groups: (1) young regular cycling women (<35 years old), older women (>35 years) with (2) regular or (3) irregular menstrual cycles, and (4) postmenopausal women. Gonadotropin-releasing hormone stimulation tests (100 μg intravenous gonadotropin-releasing hormone) were performed in the National Institute of Mental Health outpatient clinic during the follicular phase of the menstrual cycle or randomly in postmenopausal women. RESULTS: Perimenopausal women had baseline follicle-stimulating hormone and luteinizing hormone levels and stimulated follicle-stimulating hormone levels (area under the curve) that were similar to those of postmenopausal women and significantly greater than those of control (younger and older) women. Postmenopausal women had significantly greater baseline levels of luteinizing hormone bioactivity than did the other three groups. The bioactivity/immunoactivity ratio in the postmenopausal women was significantly greater than those in the perimenopausal and older cycling women, which were similar. No change in the bioactivity/immunoactivity ratio was seen after gonadotropin-releasing hormone stimulation in any group. CONCLUSIONS: Although the perimenopause is associated with increases in baseline and stimulated gonadotropin levels similar to those seen after the menopause, significantly increased baseline luteinizing hormone bioactivity and the bioactivity/immunoactivity ratio are seen only after the menopause. (Am J Obstet Gynecol 1996;175:643-50.)

A Single-sample, Subcutaneous Gonadotropin-releasing Hormone Test for Central Precocious Puberty

We compared a rapid, subcutaneous (SQ), single-sample gonadotropin-releasing hormone (GnRH) stimulation test with the standard multiple-sample, intravenous (IV) GnRH stimulation test used in the evaluation of central precocious puberty (CPP). We evaluated 22 patients presenting with evidence of precocious puberty. GnRH (100 microg) was administered subcutaneously in the clinic setting with single serum luteinizing hormone (LH) measured 40 minutes after injection. A standard IV GnRH stimulation test was performed within 2 weeks, with serum LH obtained at 0, 20, 40, and 60 minutes. LH was assayed by immunochemiluminometric assay. The mean peak LH levels after IV and SQ testing were identical. A significant correlation (r = .88) was found between the LH determined by SQ stimulations and the peak LH determined by IV GnRH testing. CPP was diagnosed (LH, >/- 8 IU/L) by both SQ and IV testing in 7 of 22 patients and was excluded by both tests in 14 of 22 patients. A diagnostic discrepancy between peak IV and SQ results was seen in 1 patient. We conclude that mean GnRH-stimulated LH levels from rapid SQ and standard IV testing are indistinguishable and that individual LH levels by each method are strongly correlated. A rapid SQ GnRH test is a valid tool for laboratory confirmation of CPP.

Normal ranges for immunochemiluminometric gonadotropin assays

Objective: We sought to establish normative data for spontaneous and gonadotropin-releasing hormone (GnRH)-stimulated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels measured by new immunochemiluminometric assays (ICMA) in children and adolescents. Methods: Random serum samples were obtained from 375 normal subjects (0.1 to 17.7 years, 230 female subjects). Intravenous GnRH stimulation tests were performed in 41 normal subjects (4.8 to 18 years, 20 female subjects). Normal ranges were calculated by age and Tanner stage. Immunochemiluminometric assays of LH and FSH concentrations were compared with levels obtained by a sensitive immunofluorometric assay and a less sensitive radioimmunoassay. Results: Random gonadotropin concentrations in normal children followed the pattern of transient elevation in infancy, low but measurable prepubertal levels, and markedly increased values at puberty. Spontaneous LH levels were higher in male infants but were not statistically different in boys and girls after infancy. Mean prepubertal LH was 0.04 ± 0.04 IU/L (n = 66), rising 100-fold during puberty. Spontaneous FSH levels were much higher than LH values, were higher in female infants, and rose threefold at puberty. Peak GnRH-stimulated LH was identical in prepubertal boys and girls (1.8 ± 1.3 IU/L, n = 17) and increased 20-fold at puberty. Mean peak GnRH-stimulated FSH was highest in prepubertal female subjects. Luteinizing hormone values measured by ICMA and immunofluorometric assay were highly correlated, but radioimmunoassay levels diverged markedly from ICMA levels at lower concentrations. Because absolute levels were higher, FSH values correlated adequately in the three assays throughout the normal physiologic range. Conclusions: Measurement of LH by ICMA is much more sensitive than older assay methods. Spontaneous LH can be accurately measured by ICMA to the very low levels present in normal prepubertal children, providing a potentially important biochemical discriminator of pubertal status. An ICMA GnRH-stimulated LH level greater than 5 IU/L is suggestive of maturing gonadotropin secretion. The ICMA LH assays provide significant enhancement in sensitivity; these assays should be used when levels may be low, and by their accuracy may reduce the time and expense of testing procedures. (J P EDIATR 1995;127:40-6)

Spontaneous serum gonadotropin concentrations in the evaluation of precocious puberty

Objective: We assessed the utility of spontaneous and gonadotropin-releasing hormone (GnRH)-stimulated serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels measured by new immunochemiluminometric assays in the evaluation and monitoring of precocious puberty. Methods: We evaluated serum gonadotropin values from intravenous GnRH stimulation tests in 49 girls with clinical signs suggesting central precocious puberty (CPP). Because GnRH-stimulated LH has been considered the standard for diagnosing CPP, we used it as the basis for comparison with GnRH-stimulated FSH levels and spontaneous LH and FSH measured by immunochemiluminometric assay. Results: Twenty-six patients had a peak serum LH value above the +2 SD threshold for normal prepubertal female subjects (LH > 5 IU/L). The GnRH-stimulated FSH values had a narrow range and did not discriminate patients with CPP. In contrast, elevations in spontaneous LH and FSH were found to be specific for CPP. Spontaneous LH levels correlated strongly with peak stimulated LH levels in subjects with precocious puberty ( r = 0.79) or in control subjects ( r = 0.93, both p < 0.0001). Spontaneous LH levels in excess of 0.1 IU/L detected true puberty with 94% sensitivity and 88% specificity. Random LH levels in excess of 0.3 IU/L had 100% specificity for CPP. Conclusions: The GnRH-stimulated FSH levels do not adequately differentiate children with and without CPP and have limited utility in the evaluation of precocious puberty. Spontaneous FSH levels are elevated in CPP with fair sensitivity and marked specificity. Elevated random LH, measured by third-generation assay such as immunochemiluminometric assay, is strongly correlated with and highly predictive of elevated peak GnRH-stimulated LH, and is a useful screening tool for CPP. (J P EDIATR 1995;127:47-52)