Leuprolide MOA (Mechanism of action of Leuprolide Acetate)

0
400
leuprolide agonist activity leuprolide moa
Persistent stimulation of the pituitary gland causes the inhibition of gonadotropins

Leuprolide MOA (Mechanism of action of Leuprolide) is discussed here in detail. Leuprolide Acetate is used as monotherapy or in combination with norethindrone for the treatment of various conditions listed below:

  • Leuprolide acetate monthly depot injection is used for the palliative treatment of advanced prostatic carcinoma.
  • For the treatment and prevention of recurrence of Endometriosis. It may also be used to relieve the symptoms associated with endometriosis and to reduce the size of endometriotic lesions.
  • It is used to reduce the bleeding associated with uterine fibroids especially in the pre-operative period.
  • Precocious puberty due to a pituitary cause manifesting as the onset of secondary sexual characteristics below the age of puberty typically at the age of 8 or 9 years or younger. Children may also have advanced bone age.
  • It is also being used as an off-label medicine for the suppression of ovarian hormones in patients with advanced metastatic breast cancer, as hormonal therapy in transgender females, and for the treatment of paraphilias (sexual perversion behaviors).

Leuprolide MOA (Mechanism of action of Leuprolide):

All the indications of Leuprolide discussed above have one thing in common – these disorders are dependent on sex steroids hormones.

Sex Steroid hormones are:

  • Androgens (Testosterone) in males
  • Estrogens and Progesterone in females.

How are androgens and female sex steroids secreted in the human body?

Sex steroids are synthesized in the human body in the genital organs. In males, the testes synthesize the androgens, while the estrogens and progesterone are synthesized by the ovaries.

The pituitary gland is the master gland that controls most of the endocrine glands in the human body. The gonadotrophic cells of the anterior pituitary hormone release the gonadotropins, the LH (Leuteinzining hormone), and FSH (Follicle-stimulating hormone).

The hypothalamus releases GnRH, stimulating the pituitary gland to release gonadotropins (LH and FSH) which in turn stimulate the synthesis and release of Sex steroids (androgens, estrogen, and progesterone).

Gonadotrophins stimulate the synthesis of androgens in males and estrogens and progesterone in females. These sex steroids, in turn, cause the negative feedback inhibition of gonadotrophins.

The gonadotropins (LH and FSH) produced in the pituitary gland are stimulated by the hypothalamic hormone, gonadotropin-releasing hormone (GnRH), and inhibited by the sex steroids (androgens, estrogen, and progesterone). However, the GnRH stimulates the pituitary gland in a pulsatile manner.

It is important to note that pulsatile secretion of GnRH causes the stimulation of gonadotropins while a continuous stimulation by the GnRH causes the inhibition of gonadotropins.

Leuprolide acetate is a GnRH agonist

Leuprolide Acetate causes the persistent stimulation of pituitary gonadotrophs. This causes an increase in the release of LH and FSH transiently, however, persistent stimulation results in the inhibition of LH and FSH.

Persistent stimulation of the pituitary gland by leuprolide causes the inhibition of gonadotropins.

Inhibition of gonadotropins causes a decrease in the stimulation of ovaries and testes. The ovarian hormones (estrogens and progesterone) and testicular androgen secretion are in turn inhibited.

The sex-steroid-dependent organs are deprived of the stimulatory effects of the hormones. This effect is especially important in patients with advanced prostatic and breast cancers. These two organs are primarily dependent on sex steroids. Patients should be monitored when the treatment is initiated for a flare-up of the disease as Leuprolide causes the transient elevation of the sex steroids.

Likewise, a decrease in the synthesis of androgens is also required in children with precocious puberty to reduce the accelerated growth and virilization. Leuprolide also inhibits the growth of uterine leiomyomas (fibroids).

In Summary:

Leuprolide MOA causing a reduction in the androgens and ovarian hormones is due to the non-pulsatile stimulation of gonadotropins. This non-pulsatile stimulation causes a paradoxical inhibition of gonadotropins.