Gonadorelin Acetate Injection

Male infertility is a critical issue in the global field of reproductive health, with an incidence rate of approximately 10% to 15% among childbearing couples, and male factors accounting for 40% to 50% of all infertility cases. The pathogenesis of this disease is complex, mainly associated with hypothalamic-pituitary-gonadal (HPG) axis dysfunction, spermatogenic disorders and hormonal imbalances. Among these, spermatogenic disorders caused by central gonadal dysfunction have become a key focus and difficulty in clinical diagnosis and treatment due to their insidious onset and high treatment complexity. As a synthetic injectable GnRH formulation, Gonadorelin Acetate Injection effectively avoids gastrointestinal degradation and loss of oral drugs by virtue of its core advantages of rapid onset, strong targeting, controllable dosage and high bioavailability. It has thus become a core drug for regulating male reproductive endocrinology and improving spermatogenic function, playing an irreplaceable role especially in the treatment of male infertility caused by central factors.

The product is a polypeptide hormone injectable, whose core component gonadorelin acetate is highly homologous in structure to endogenous GnRH secreted by the human hypothalamus, with high purity and strong biological activity. Common clinical formulations include sterile injection solutions and lyophilized powder for injection, which must be stored in the dark under refrigeration at 2～8℃ to prevent the degradation of drug activity. As an injectable formulation, its most prominent advantage is the flexible and precise administration route: the drug can be delivered via subcutaneous or intravenous injection, is rapidly absorbed by the body, and reaches the peak plasma concentration in approximately 3 minutes with a half-life of about 6 minutes. It is rapidly metabolized and excreted by the kidneys with no obvious accumulation, and the administration dosage and frequency can be precisely adjusted according to the patient's condition to achieve individualized treatment.

In the treatment of male infertility, its mechanism of action is strictly centered on the regulation of the HPG axis: after injection, the drug specifically binds to GnRH receptors in the anterior pituitary gland and stimulates the pituitary to secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH) through positive feedback regulation. Among these, LH mainly acts on Leydig cells in the testes to promote the synthesis and secretion of testosterone-a hormonal prerequisite for spermatogenesis and sperm maturation, effectively improving testicular hypoplasia and low testosterone levels. FSH directly acts on Sertoli cells in the seminiferous tubules of the testes, regulating the proliferation, differentiation and maturation of spermatogenic cells, promoting spermatogenesis, and increasing sperm count, motility and the rate of morphologically normal sperm.

(1) Infertility Caused by Idiopathic Hypogonadotropic Hypogonadism (IHH)
IHH is a rare congenital disease with an incidence rate of approximately 1 to 10 per 100,000 live births. It is mainly caused by insufficient synthesis and secretion of GnRH by the hypothalamus or defective pituitary response to GnRH, leading to a significant reduction in LH and FSH secretion, which in turn causes testicular hypoplasia (testicular volume ＜4ml) and low testosterone levels (＜3.5nmol/L). Clinical manifestations include non-obstructive azoospermia or severe oligozoospermia, and most patients are accompanied by delayed or absent puberty (e.g., no Adam's apple, sparse pubic and axillary hair, high-pitched voice). Some patients may also have concomitant anosmia or hyposmia.

(2) Infertility Caused by Secondary Hypogonadotropic Hypogonadism
This condition is mostly caused by acquired factors, with common etiologies including pituitary surgery, cranial radiotherapy, empty sella syndrome and pituitary microadenomas. These factors lead to impaired pituitary secretion of LH and FSH, which in turn affects testicular spermatogenic function, with clinical manifestations of oligozoospermia and asthenozoospermia, and in severe cases, azoospermia. Prior to clinical treatment, pituitary reserve function must be evaluated via the GnRH stimulation test to rule out irreversible pituitary damage (e.g., pituitary atrophy after severe radiotherapy). For patients with preserved pituitary reserve function, this injection can be used for treatment to supplement insufficient GnRH, stimulate the pituitary to secrete gonadotropins, and improve spermatogenic function.

(3) Infertility Tendency Caused by Constitutional Delay of Puberty (CDP)
Constitutional delay of puberty is a benign disorder characterized by delayed pubertal onset, commonly seen in adolescent males. It is mainly manifested as transient gonadal hypofunction and immature spermatogenic function. Without timely intervention, it may lead to permanent damage to spermatogenic function and the development of infertility. Gonadorelin Acetate Injection can be used for diagnostic treatment and early intervention in such patients: short-term drug injection stimulates the pituitary to secrete gonadotropins, and observing the recovery of testicular development and spermatogenic function can effectively differentiate CDP from IHH (hormone levels increase significantly after injection in CDP patients, whereas the response is weak in IHH patients).

1. Preliminary Exploration of the Hypothalamic-Pituitary-Gonadal Axis Mechanism
In the 1930s, Harris first postulated that the function of the anterior pituitary gland is regulated by specific factors secreted by the hypothalamus, pointing out the direction for research in the field of reproductive endocrinology and serving as an important prerequisite for the discovery of gonadorelin acetate. In the decades that followed, scientists conducted in-depth research on the hypothalamic regulation of reproductive hormones, and gradually confirmed that the hypothalamus secretes an active substance that can stimulate the pituitary to release LH and FSH, thereby regulating gonadal function. However, limited by separation technology, a pure sample of this active substance was never obtained, nor was its chemical structure identified, laying only a theoretical foundation for subsequent research.

2. Successful Isolation of Natural GnRH and Its Artificial Synthesis
In 1971, two research teams led by Schally and Guillemin successfully isolated this active substance, which regulates pituitary gonadotropin secretion, from the hypothalamic tissues of pigs and sheep respectively, named it luteinizing hormone-releasing hormone (GnRH), and quickly identified its chemical structure as a decapeptide compound. This breakthrough became a key turning point in the research and development of it. In 1973, the two scientists were awarded the Nobel Prize for this achievement, further advancing GnRH-related research. In 1974, Chinese research teams also launched research on the artificial synthesis of GnRH, and under the leadership of Academician Gong Yueting, successfully synthesized GnRH and its analogs, laying a technical foundation for subsequent formulation development. In 1978, gonadorelin was first used in medical practice as an injectable formulation under the trade name Factrel, marking its official entry into clinical practice.

3. Optimization and Popularization of it Injectable Formulations
Due to the high extraction difficulty, low yield and susceptibility to protease hydrolysis of natural GnRH, it could not meet the demand for large-scale clinical application. Scientists thus shifted their focus to the research and development of synthetic derivatives, and it was born against this background. Through structural modification of natural GnRH, it retains the original biological activity while improving stability. In 2007, domestic enterprises launched special research on gonadorelin, established professional teams to overcome challenges in raw material synthesis and formulation technology, and completed a series of research work including pharmacology, toxicology and clinical trials. In 2010, the domestically developed it raw material and its injectable formulations (water injection, powder injection) were approved as the national Class III new veterinary drugs, officially realizing localized production.