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Leuprolide

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Leuprolide is a gonadotropin releasing hormone (GnRH) agonist. When given in a pulsatile fashion leuprolide stimulates the GnRH receptors in the anterior pituitary resulting in stimulation of LH and FSH which then stimulate the ovaries and testes to produce sex steroids. Leuprolide can act as a potent inhibitor of gonadotropin secretion when administered continuously. This inhibition of gonadotropins (LH and FSH) results in suppression of ovarian and testicular production of sex steroids. Pulsatile release of leuprolide is used to treat infertility. Continuous administration of leuprolide is used to treat prostate cancer, precocious puberty, uterine fibroids and endometriosis. Because it can ultimately inhibit sex steroid production when given in a continuous manner, leuprolide can send antiandrogenic effects such as decreased libido, nausea/vomiting and symptoms of menopause like amenorrhea and hot flashes.
10 KEY FACTS
MECHANISM
GnRH Agonist (Pulsatile Use)
Gopher Dragonist (on Pulsing-track)

Leuprolide is a GnRH agonist. When given in a pulsatile fashion it binds to the GnRH receptors in the anterior pituitary which results in increased production and release of FSH and LH from the anterior pituitary.

GnRH Antagonist (Continuous Use)
Gopher Ant-toga (on Continuous-track)

Leuprolide normally works as a GnRH agonist. But when given continuously, this constant stimulation of the GnRH receptors by a GnRH agonist results in a downregulation of the GnRH receptors, resulting in a downregulation of FSH and LH. This subsequent downregulation of GnRH receptors and downregulation of FSH and LH is why Leuprolide is considered to have antagonistic effects when given continuously.

Upregulates FSH And LH
Up-regulating-arrow with Fish and Luge

GnRH binding to its receptor in the anterior pituitary upregulates production and release of FSH and LH which then bind to their receptors on the Sertoli cells and the Leydig cells respectively in males, and to the Granulosa cells and Theca internal cells respectively in females.

Downregulates FSH And LH
Down-regulating-arrow with Fish and Luge

Constant stimulation of the GnRH receptors by a GnRH agonist results in a downregulation of the GnRH receptors, resulting in a downregulation of FSH and LH.

INDICATIONS PULSATILE
Infertility
Infertile-female-plant

When given in a pulsatile fashion, Leuprolide upregulates FSH and LH. Increasing LH stimulates leydig cells to produce testosterone and thereby increases sperm production.

INDICATIONS CONTINUOUS
Prostate Cancer
Prostate-plum Tumor-guy

Leuprolide is approved for palliative treatment of advanced prostate cancer. In addition to prostate cancer, Leuprolide can also be used for breast cancer.

Precocious Puberty
Pubescent-baby

Precocious puberty is the appearance of hormonal and physical signs of puberty at a younger age than what is considered normal. Central precocious puberty can ben treated by suppressing LH and FSH production by the anterior pituitary and thereby suppressing sex steroid production. Precocious puberty can be treated with continuous leuprolide because when given in a continuous fashion leuprolide acts as a GnRH antagonist, ultimately resulting in decreased production of sex steroids.

Uterine Fibroids
Uterus Fiber-net

GnRH agonists can be used to treat fibroids when they are given in a continuous manner resulting in downregulation of the GnRH receptors and there by decreasing LH and FSH and thus decreasing the production of estrogen and progesterone, which temporarily puts the patient in a postmenopausal state. This results in the shrinking of fibroids and the cessation of menstruation.

Endometriosis
Endometrium-roses

Endometriosis is a condition in which cells from the lining of the uterus (endometrium) appear and flourish outside the uterine cavity, most commonly on the membrane lining the abdominal cavity, peritoneum. When GnRH is given continuously it results in downregulation of the GnRH receptors and subsequent downregulation of LH and FSH. This decrease in LH and FSH significantly decreases estrogen; it is this decrease in estrogen that helps control symptoms in endometriosis.

SIDE EFFECTS
Anti-androgenic Effects
Ant-tie and Android-genie

Leuprolide has antiandrogenic effects, such as decreasing testosterone in men and estrogen in women. This manifests as decreased libido, nausea/vomiting, as well as hot flashes and amenorrhea (in women).

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