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Gnr4.0

Gonadorelin – Forschung

Überwiegend Mechanismus / Beobachtung

11 begutachtete Studien

Was die Evidenz sagt

Überwiegend Mechanismus / Beobachtung

Die meisten Studien zu Gonadorelin sind mechanistisch oder beobachtend statt RCTs, die einen klinischen Effekt messen — betrachte die Ergebnisse als vorläufig.

Die meiste Evidenz stammt aus gemischt-qualitativen Studien, veröffentlicht 1988–2024 mit einer typischen Studiengröße von 76 Teilnehmenden.

Basierend auf 11 Studien · 2,014 Teilnehmende insgesamt

Konfidenz

Geringe Konfidenz

Nach Outcome

GnRH axis, gonadotropins & diagnostic testing
Überwiegend Mechanismus / Beobachtung11 Studien
Fertility & ovulation inductionPulsatiles GnRH über Pumpe löst bei hypothalamischer Amenorrhoe zuverlässig Ovulation und Schwangerschaft aus; pulsatiles GnRH induziert bei hypogonadotropen Männern die Spermatogenese · Wochen bis Monate
Überwiegend Mechanismus / Beobachtung9 Studien
Women's health
Überwiegend Mechanismus / Beobachtung3 Studien
Men's vitality & testicular function
Zu wenige bewertete Studien2 Studien
Safety profile
Zu wenige bewertete Studien1 Studie

Stetige Forschung

3 Studien in den letzten 5 Jahren

198820062024

1Beobachtungsstudien=76 · small study2002

Pulsatile GnRH therapy in IHH men is very successful in inducing androgen production and spermatogenesis.

Pitteloud N, Hayes FJ, Dwyer A, Boepple PA, Lee H, Crowley WF Jr. · J Clin Endocrinol Metab (2002)

76 men with idiopathic hypogonadotropic hypogonadism given pulsatile GnRH 5-25 ng/kg per pulse sc, titrated to normal testosterone, for 12-24 months
LH normalized in 97% and testosterone in 93%; men with some prior pubertal development reached normal testicular size, FSH, inhibin B, and sperm in 92-100%
Men with no prior puberty did worse — sperm counts plateaued (median 3 million/ml) and 18% stayed azoospermic

Quelle ansehen

2Übersicht2019

Fertility can be induced with pulsatile GnRH treatment or gonadotropin regimens in most patients.

Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N. · Endocr Rev (2019)

Comprehensive review of congenital hypogonadotropic hypogonadism (including Kallmann syndrome) — diagnosis, genetics, and management
Reproductive capacity depends on pulsatile GnRH secretion; treatment can induce puberty and, in most patients, fertility
Notes ~10-20% of male patients show spontaneous reversal of their hypogonadotropic hypogonadism

Quelle ansehen

3Beobachtungsstudien=71 · small study1993

Pulsatile GnRH, when compared to exogenous gonadotropins, results in high rates of ovulation and conception, but a decreased risk of multiple folliculogenesis, higher order multiple gestations, and ovarian enlargement.

Martin KA, Hall JE, Adams JM, Crowley WF Jr. · J Clin Endocrinol Metab (1993)

Retrospective comparison: 41 women / 118 cycles of pulsatile GnRH (IV, 75-250 ng/kg) vs 30 women / 111 cycles of exogenous gonadotropins for hypogonadotropic amenorrhea
Ovulation and conception rates per cycle were similar, but cumulative conception after six cycles appeared higher with pulsatile GnRH (96% vs 72% by life-table analysis)
Pulsatile GnRH produced fewer multiple follicles (18.9% vs 47.6% of cycles with >2 follicles), lower multiple-gestation risk (8.3% vs 14.8%), and less ovarian enlargement

Quelle ansehen

4Übersicht1990

When used appropriately, pulsatile GnRH is safe, effective, and offers an excellent alternative to conventional gonadotropin therapy for women with disordered endogenous GnRH secretion.

Martin K, Santoro N, Hall J, Filicori M, Wierman M, Crowley WF Jr. · J Clin Endocrinol Metab (1990)

Clinical review of pulsatile GnRH therapy for ovulatory disorders, drawing on the Massachusetts General Hospital experience
High ovulation and conception rates in complete GnRH deficiency and hypothalamic amenorrhea; lower rates in PCOS
Recommends ~75 ng/kg starting dose and a physiologic pulse frequency; can be run in the office without on-line estradiol monitoring

Quelle ansehen

5Beobachtungsstudien=1,492 · large study2021

The 60-minute LH/FSH ratio yielded the highest consistency, with an area under the ROC curve (AUC) of 0.988.

Cao R, Liu J, Fu P, Zhou Y, Li Z, Liu P. · Front Endocrinol (Lausanne) (2021)

Retrospective diagnostic study of 1,492 girls (518 with idiopathic central precocious puberty) undergoing GnRH-analogue stimulation testing
The 60-minute post-stimulation LH/FSH ratio had excellent discrimination (AUC 0.988; cutoff 0.603, sensitivity 97.3%, specificity 93.0%)
A basal LH >0.535 mIU/L could diagnose CPP without a stimulation test in many cases

Quelle ansehen

6Übersicht2024

In cases of severe CHH, all 3 waves of GnRH pulsatility are absent.

Rohayem J, Alexander EC, Heger S, Nordenström A, Howard SR. · Endocr Rev (2024)

Review of the hypothalamic-pituitary-gonadal axis's three physiological activity waves (fetal, mini-puberty, puberty) and their disruption in congenital hypogonadotropic hypogonadism
Explains why absent GnRH pulsatility impairs testicular maturation and later fertility, motivating replacement therapy
Notes evidence from small case series that hormonal replacement mimicking mini-puberty can normalize testis/penile size and aid testis descent

Quelle ansehen

7Beobachtungsstudien=37 · small study1988

Pulsatile GnRH was safe and very successful in induction of pregnancy in [hypothalamic amenorrhoea].

Gompel A, Mauvais-Jarvis P. · Hum Reprod (1988)

37 women with hypothalamic amenorrhea treated with IV pulsatile GnRH over 117 cycles
42 pregnancies achieved (within a mean of 2.3 cycles), with only four treatment failures
One twin pregnancy and no ovarian hyperstimulation observed

Quelle ansehen

8Beobachtungsstudien=12 · very small study2017

All the patients had documented ovulation, after a mean of 17 days on pump stimulation.

Christou F, Pitteloud N, Gomez F. · Gynecol Endocrinol (2017)

12 women with amenorrhea of hypothalamic origin (Kallmann syndrome, isolated hypogonadotropic hypogonadism, functional hypothalamic amenorrhea) treated with pulsatile GnRH every 90 minutes (IV 5 µg/pulse or sc 15 µg/pulse)
All patients ovulated (single ovulation in 30 of 33 cycles), yielding 10 pregnancies across 7 patients
A comparison PCOS patient showed a premature LH surge without ovulation — reinforcing that PCOS responds poorly

Quelle ansehen

9Beobachtungsstudien=92 · small study2015

Pulsatile GnRH requires a shorter time for initiation of spermatogenesis than gonadotropin therapy in IHH male patients.

Huang B, Mao J, Xu H, Wang X, Liu Z, Nie M, Wu X. · Zhonghua Yi Xue Za Zhi (2015)

Retrospective comparison in 92 men with idiopathic hypogonadotropic hypogonadism: pulsatile GnRH (n=40) vs hCG/hMG gonadotropins (n=52)
Spermatogenesis success rate 50.0% with pulsatile GnRH vs 28.8% with gonadotropins (P=0.038)
Pulsatile GnRH reached initial sperm appearance faster (6.5 vs 10.8 months, P=0.001)

10Übersicht2021

Sexual maturation and reproductive function depend on the pulsatile secretion of GnRH.

Bettocchi C, Rinaldi M, Sebastiani F. · Curr Pharm Des (2021)

Focused review of GnRH therapy in hypogonadotropic hypogonadism, examining effects on fertility and cognition
Reiterates that reproductive function depends on pulsatile (not continuous) GnRH delivery
Synthesizes the current evidence level for GnRH as a treatment regimen in this condition

Quelle ansehen

11Beobachtungsstudien=234 · medium study2018

In girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation.

Lee HY, Lee YJ, Ahn MB, Cho WK, Suh BK. · Ann Pediatr Endocrinol Metab (2018)

234 girls with idiopathic central precocious puberty diagnosed by a peak LH >5.0 U/L on the gonadorelin stimulation test
Uses gonadorelin by name as the diagnostic stimulating agent — confirming the test's routine clinical role
Overweight girls had a lower peak LH (8.95 vs 11.97 U/L) and FSH after gonadorelin, with overweight negatively associated with peak LH

Quelle ansehen

In der Forschungsbibliothek ansehen

Gonadorelin – Forschung

Überwiegend Mechanismus / Beobachtung

Predictors of outcome of long-term GnRH therapy in men with idiopathic hypogonadotropic hypogonadism.

Clinical Management of Congenital Hypogonadotropic Hypogonadism.

Comparison of exogenous gonadotropins and pulsatile gonadotropin-releasing hormone for induction of ovulation in hypogonadotropic amenorrhea.

Clinical review 15: Management of ovulatory disorders with pulsatile gonadotropin-releasing hormone.

The Diagnostic Utility of the Basal Luteinizing Hormone Level and Single 60-Minute Post GnRH Agonist Stimulation Test for Idiopathic Central Precocious Puberty in Girls.

Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement.

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea.

The induction of ovulation by pulsatile administration of GnRH: an appropriate method in hypothalamic amenorrhea.

Spermatogenesis of pulsatile gonadotropin-releasing hormone infusion versus gonadotropin therapy in male idiopathic hypogonadotropic hypogonadism.

GnRH in the Treatment of Hypogonadotropic Hypogonadism.

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty.