Pulsatile Luteinizing Hormone-releasing Hormone Administration Research Articles

Predictive value of luteinizing hormone releasing hormone (LHRH) bolus testing before and after 36-hour pulsatile LHRH administration in the differential diagnosis of constitutional delay of puberty and male hypogonadotropic hypogonadism.

Intravenous LHRH bolus testing (100 micrograms) after 36 h of pulsatile LHRH administration (5 micrograms/90 min) preliminary has been reported to allow complete differentiation between constitutional delay of puberty (DP) and hypogonadotropic hypogonadism (HH) in a small group of sexually immature patients. So far, these data have never been confirmed. To assess the discriminatory power of the test, 33 patients with a presumptive diagnosis of either DP (n = 17) or HH (n = 16), confirmed by clinical follow-up, were studied accordingly. Both groups of patients had similar mean basal LH and FSH levels (P > 0.10). The mean basal plasma testosterone level was three times higher in DP than in HH (4.2 +/- 1.0 vs. 1.4 +/- 0.2 nmol/L, P* < 0.001), but there was a wide overlap. In response to the first LHRH bolus test, the mean LH increment was significantly lower in HH than in DP patients (P < 0.001), but, in 44% of the patients, the values overlapped. The FSH increments were similar in HH and DP. Pulsatile LHRH administration for 36 h similarly increased LH levels in HH and DP to values (2.7 +/- 0.4 and 3.8 +/- 0.5, respectively) slightly higher than before (P < 0.01), but again, not statistically significantly different from each other. The mean testosterone levels increased 2-fold in both groups and remained significantly higher in DP than in HH (7.6 +/- 2.1 vs. 2.8 +/- 0.5 nmol/L P* < 0.05). The mean FSH levels after priming also rose, however, to levels significantly higher in HH than in DP (5.2 +/- 0.8 vs. 3.5 +/- 0.4, P* < 0.05). In HH the ratio of FSH to LH almost doubled, whereas it virtually remained unchanged in DP. LHRH bolus testing after LHRH priming evoked a significantly lower LH response in both HH and DP than before priming despite only slightly higher baseline LH values. The LH increment in HH was five times lower in HH than in DP. In any of the 16 HH patients, the LH increment was < or = 3 IU/L, whereas in 15 out of 17 DP patients the increase was higher (sensitivity of the test 100%, specificity 88%, and diagnostic efficiency 94% after LHRH priming against 56%, 94%, and 75% respectively, before LHRH priming.(ABSTRACT TRUNCATED AT 400 WORDS)

Predictive value of luteinizing hormone releasing hormone (LHRH) bolus testing before and after 36-hour pulsatile LHRH administration in the differential diagnosis of constitutional delay of puberty and male hypogonadotropic hypogonadism

Predictive value of luteinizing hormone releasing hormone (LHRH) bolus testing before and after 36-hour pulsatile LHRH administration in the differential diagnosis of constitutional delay of puberty and male hypogonadotropic hypogonadism

Delayed puberty in uremia: pituitary-gonadal function during short-term pulsatile luteinizing hormone-releasing hormone administration.

Pubertal development is frequently delayed or disordered in children with chronic renal failure. Both neuroendocrine and peripheral alterations due to uremia have been hypothesized to explain the impairment in the pituitary gonadal axis. The aim of the present study was to evaluate quantitative (immunological) and qualitative (biological) LH secretion, as well as FSH and sex steroids, before and during 7 days of sc LHRH administration (136-150 ng/kg bw every 120 min) in 5 uremic children (13.1-14.8 yr) with delayed puberty. Six nonuremic children (13.2-17.8 yr) with delayed puberty underwent the same schedule and served as control group. On day 0 mean immunoreactive LH (I-LH) levels were higher in uremic (4.5 +/- 0.9 mIU/ml) than in nonuremic (1.9 +/- 03 mIU/ml; p < 0.05) subjects while no differences were observed in bioactive LH (B-LH) levels (2.9 +/- 0.7 mIU/ml vs 2.4 +/- 0.3 mIU/ml). In both groups of subjects testosterone was at prepubertal levels. Spontaneous I-LH and B-LH pulses were observed sporadically in both uremic and nonuremic subjects. Short-term pulsatile LHRH administration induced significant increases in B-LH, I-LH, FSH and testosterone. The B/I LH ratio increased from day 0 (0.7 +/- 0.2) to day 7 (1.3 +/- 0.4; p < 0.05) in uremics while it showed wide fluctuations in nonuremic subjects. On day 7, 4 uremic and 5 nonuremic subjects showed a pulsatile release of B-LH after exogenous LHRH pulses. Our data document that in uremia there are qualitative as well as quantitative abnormalities in pituitary gonadal secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Endogenous opioid blockade and gonadotropin secretion: role of pulsatile luteinizing hormone-releasing hormone administration in anorexia nervosa and weight loss amenorrhea

In anorexia nervosa alterations in the hypothalamic-pituitary-gonadal unit were previously thought to have been connected to an increase of endogenous opiate tone. The authors tried to prove that the replacement of normal endogenous steroid levels could restore the functional coupling between opiatergic and luteinizing hormone-releasing hormone (LH-RH) neurons in patients with anorexia nervosa. Pulsatile LH-RH therapy has been used to achieve normal ovarian activity. The authors studied gonadotropin levels before and during intravenously (IV) pulsatile LH-RH therapy (50 to 100 ng/kg body weight/90 to 120 minutes) in three anorexia nervosa and two weight loss amenorrhea patients, during both placebo and naloxone administration (2 mg IV bolus plus 4 mg infusion lasting 120 minutes). Before therapy, naloxone administration did not significantly change gonadotropin levels in three out of five patients, while a decrease in gonadotropin levels was observed in the other two subjects. During LH-RH therapy, normal pituitary-gonadal activity was demonstrated and ovulatory cycles were found in all patients. Naloxone administration did not change gonadotropin release during LH-RH therapy. Data could support the hypothesis of either a primitive impairment of LH-RH neurons, or an alteration in central regulation of LH-RH pulsar in anorexia nervosa.

Short-term pituitary desensitization to luteinizing hormone-releasing hormone (LH-RH) after pulsatile LH-RH administration in women with amenorrhea of suprapituitary origin

The existence of a short-term pituitary desensitization in luteinizing hormone (LH) release to single doses of luteinizing hormone-releasing hormone (LH-RH) in the ovariectomized rat was recently disclosed. The purpose of the present study was to investigate whether this refractoriness is also present in humans. Blood from six women with amenorrhea of suprapituitary origin was sampled every 10 minutes for 300 minutes for determination of LH and follicle-stimulating hormone (FSH). A pulse of 20 micrograms LH-RH was given intravenously 90 and 210 minutes after the first blood sample, and 2 micrograms LH-RH was given 30, 150, 240, and 270 minutes after t0. The mean maximal increments of LH and FSH were compared. The LH response to a 2-micrograms LH-RH bolus given 30 (t240) or 60 (t150) minutes after a 20-micrograms LH-RH pulse was significantly decreased, compared with the initial response to this dose at t30. For both LH and FSH, the response to 2 micrograms LH-RH given 30 minutes after the 20-micrograms pulse (t240) was almost absent, compared with 60 (t150) minutes after the 20-micrograms dose. We conclude that a short-term pituitary refractoriness to LH-RH is present after administration of single pulses of LH-RH in women with amenorrhea of suprapituitary origin and pulses of LH-RH in the physiologic range (2 micrograms) given to these women do not always generate LH and FSH increments that are identifiable as significant hormone pulses.

Increased frequency of pulsatile luteinizing hormone-releasing hormone administration selectively decreases follicle-stimulating hormone levels in men with idiopathic azoospermia

Men with idiopathic azoo-oligospermia and selective elevations of follicle-stimulating hormone (FSH) levels have evidence for decreased luteinizing hormone-releasing hormone (LH-RH) pulse frequency. We assessed whether increasing the frequency of pulsatile LH-RH stimulation can lower FSH levels in such men. We administered 5.0 microgram of pulsatile LH-RH subcutaneously at intervals of 30, 60, and 120 minutes for 1 week to four men who had azoospermia, elevated FSH levels, and normal LH and testosterone (T) levels. The order of administration was varied among subjects. Frequent blood samples were obtained for 6 hours before LH-RH treatment and during the last 6 hours of each regimen. Before LH-RH treatment, the FSH levels (mean +/- standard error of the mean) were 359 +/- 18 ng/ml (normal range, 30 to 230 ng/ml). During LH-RH treatment, FSH levels progressively declined from 397 +/- 68 ng/ml to 237 +/- 70 ng/ml to 175 +/- 43 ng/ml as the frequency of administration increased from every 120 to 60 to 30 minutes, respectively (P less than 0.05). Unlike the FSH levels, which showed a progressive decline, LH, T, and estradiol levels showed no consistent relationship to LH-RH pulse frequency. We conclude that (1) in men with idiopathic azoospermia and elevated FSH levels, it is possible to decrease FSH levels by increasing the frequency of pulsatile LH-RH stimulation; (2) this decline does not appear to be a result of changes in steroid feedback or pituitary down-regulation; and (3) the frequency of pulsatile LH-RH stimulation can differentially modulate LH and FSH secretion by the pituitary gland.

NIH conference. Therapeutic applications of luteinizing-hormone-releasing hormone and its analogs.

The chemical structure of luteinizing-hormone-releasing hormone (LHRH) was discovered in 1971 after more than a decade of intensive effort. Subsequent physiologic studies in primates and humans showed that the biologic activity of LHRH depends on the way in which the hormone is administered. Pulsatile administration of LHRH, which mimics the natural secretory pattern, causes sustained secretion of the gonadotrophins. This method of administration has been used to induce ovulation in women with hypothalamic amenorrhea and to induce puberty and spermatogenesis in men with hypogonadotrophic hypogonadism. Continuous infusion, however, produces only transient stimulation of gonadotrophin secretion, followed by a "desensitization" response in which gonadotrophin secretion is inhibited. Thus, LHRH can either augment or inhibit gonadotrophin secretion depending on the mode of administration. Recently, long-acting synthetic analogs of LHRH have been shown to desensitize the pituitary gland and inhibit gonadotrophin release when administered as a single daily subcutaneous injection. These LHRH analogs have proved highly effective in the treatment of prostatic carcinoma and central precocious puberty. They are also being studied as a new approach to contraception and to the treatment of endometriosis and polycystic ovary syndrome.

Pituitary gonadotropin responses to different modes and doses of intravenous luteinizing hormone-releasing hormone administration in normal men

In 22 potentially fertile men, pituitary gonadotropin secretion was investigated by intravenous luteinizing hormone-releasing hormone (LH-RH) administration. LH-RH was administered continuously (1 microgram/minute) and in a pulsatile fashion (20 micrograms at 20-minute intervals, 20 micrograms at 60-minute intervals, and 60 micrograms at 60-minute intervals), for 3 hours, under standardized conditions. Blood was collected continuously by means of an integrated sampling technique. The mean serum luteinizing hormone (LH) concentration after any type of pulsatile administration rose significantly more than after continuous LH-RH administration. The mean increase in LH after pulsatile LH-RH administration with a 60-micrograms dose and 60-minute intervals was significantly greater than after pulsatile administration with a 20-micrograms dose and 20- or 60-minute intervals. No differences were observed in follicle-stimulating hormone responses after any type of LH-RH administration. These data confirm the existence of a self-priming effect for LH in the men; and maximum pituitary stimulation, within the dosage range tested, is reached after pulsatile LH-RH stimulation with an interval of 60 minutes.

The effect of pulsatile and continuous intravenous luteinizing hormone-releasing hormone administration on pituitary luteinizing hormone and follicle-stimulating hormone release in normal men

In 14 healthy, potentially fertile men, pituitary gonadotropin responses were studied under standardized conditions. Luteinizing hormone-releasing hormone (LH-RH) was given as a continuous infusion of 1 microgram/minute for 4 hours or in a pulsatile fashion with 20 micrograms as an intravenous bolus at intervals of 20 minutes for 4 hours. Blood was collected continuously by means of an integrated sampling technique. The mean serum luteinizing hormone (LH) concentration showed an oscillating pattern around a plateau level reached within 45 minutes during continuous LH-RH administration. During pulsatile infusion, an identical pattern for the first 45 minutes was observed with, thereafter, a continuous increase from 105 minutes until the end of the infusion. The mean increase in the serum LH level during pulsatile administration was significantly higher (P = 0.00001) than the mean increase seen during continuous infusion. The follicle-stimulating hormone concentration revealed a gradual progressive increase after both methods of stimulation, without a significant difference in the mean increase between the two types of administration. This study demonstrates the existence of a self-priming effect of LH after pulsatile LH-RH administration in the man like that in the woman.