Leuprorelin Tablet

The core therapeutic effect of Leuprorelin Tablet derives from its precise regulation of the hypothalamic‑pituitary‑gonadal (HPG) axis. Through specific action on pituitary GnRH receptors, it achieves bidirectional regulation of endogenous sex hormone levels and ultimately produces a medical castration effect, laying the foundation for the treatment of sex hormone‑dependent diseases.
Its mechanism of action mainly involves two key steps: competitive receptor binding and hormonal regulation. These two steps are interrelated and progressive, ensuring stable and long‑lasting drug action. In line with the characteristics of the oral sustained‑release formulation, it reduces adverse reactions caused by hormonal fluctuations.

(1) Competitive Binding to Pituitary GnRH Receptors
Natural GnRH is secreted by the hypothalamus. Its main function is to bind to GnRH receptors on the anterior pituitary, stimulating the secretion of luteinizing hormone (LH) and follicle‑stimulating hormone (FSH), which in turn regulate ovarian or testicular function and promote the synthesis and secretion of estradiol and testosterone.
The active ingredient of the product, leuprorelin acetate, is a highly active synthetic GnRH analog. It shares high structural similarity with natural GnRH, but its affinity for pituitary GnRH receptors is more than 100‑foldhigher than that of natural GnRH. Moreover, it is resistant to enzymatic hydrolysis and has a longer duration of action, which constitutes the chemical basis for its long‑acting therapeutic effect.
After oral sustained‑release absorption, circulating leuprorelin acetate preferentially binds competitively to pituitary GnRH receptors, occupying binding sites and preventing natural GnRH from interacting with its receptors.

Compared with other leuprorelin formulations, the sustained‑release technology of ir enables slow and stable drug release, avoiding the burst release seen with injectable formulations. This reduces the intensity and duration of the flare reaction, minimizes clinical discomfort caused by sharp hormonal fluctuations, and improves patient tolerability, especially for long‑term therapy.
(2) Hormonal Regulation and Tumor‑Suppressive Effects
After achieving medical castration via competitive GnRH receptor binding, the product exerts its core effect by regulating systemic hormone levels, particularly blocking ovarian estrogen synthesis and secretion, thereby inhibiting the growth of estrogen receptor‑positive breast cancer cells. This represents its key therapeutic pathway in premenopausal breast cancer.

Following long‑term administration of it, pituitary LH and FSH are significantly reduced. Ovarian function is suppressed due to the loss of gonadotropic stimulation, leading to a marked decrease in estrogen synthesis and secretion, eventually falling to postmenopausal levels (estradiol <20 pg/ml).
In estrogen receptor‑positive breast cancer, abundant estrogen receptors are present on tumor cell surfaces. Sustained circulating estrogen binds to these receptors, activating proliferative signaling and accelerating tumor growth, invasion, and metastasis.
By lowering systemic estrogen levels, Leuprorelin Tablet reduces estrogen‑receptor binding, blocks proliferative signaling, and inhibits tumor cell growth, even leading to tumor shrinkage or regression. Stable hormonal regulation also reduces estrogen's impact on the tumor microenvironment, lowers metastatic risk, and creates favorable conditions for subsequent combination therapy.

Based on its core mechanisms of medical castration and hormonal regulation, the product is mainly used for the treatment of various sex hormone‑dependent diseases. Premenopausal breast cancer (estrogen receptor‑positive patients) is its primary indication. It is also indicated for prostate cancer, endometriosis, uterine fibroids, central precocious puberty, and other conditions.
Dosage regimens and therapeutic objectives vary across indications. Leveraging its advantages of oral convenience and stable efficacy, it provides individualized treatment options for diverse patient populations.

Resistance is complex and mainly involves three interacting factors:
1. Alteration of drug targetsLong‑term use downregulates pituitary GnRH receptor expression or induces receptor mutations, reducing binding efficiency. Gonadotropin secretion is no longer sufficiently inhibited; estrogen and testosterone rebound, re‑stimulating tumor growth.
2. Abnormal signal transduction pathways
◦ Pituitary MAPK/ERK pathway activation bypasses GnRH control and autonomously promotes LH/FSH secretion.
◦ Tumor PI3K/Akt pathway activation allows estrogen‑independent proliferation, even at low estrogen levels.
3. Increased drug eliminationEnhanced hepatic cytochrome P450 activity accelerates metabolism; increased renal clearance reduces plasma concentrations. Half‑life shortens and effective levels cannot be maintained.