Synthetic preparations of

gonadotrophins
By DR SHUMAILA KANWEL
 Learning objectives
• What are Syhthetic preparations of gonadal
hormones?
• What are their therapeutic uses and adverse
effects?
• What are GnRH agonist?
• Explain their MOA , therapeutic uses &
adverse effects?
 Gonadotropins
• The gonadotropins(FSH and LH) are produced
by a single type of pituitary cell,
gonadotropes.
• In women, the principal function of FSH is to
direct ovarian follicle development.
• Promotes estrogen secretion
• In males FSH promotes sperm developement
• .
 Leuteinizing Hormone(LH)

• In Females
• Stimulates ovulation
• Promotes secretion of estrogen and
progesterone by ovaries
• In males
• LH stimulates production of testosterone
Both FSH and LH are needed for ovarian
steroidogenesis.
 Gonadotropins preparations
• Menotropins(mixture of FSH and LH)
• FSH & its analogue
• Urofollitropin
Follitropin alpha
Follitropin beta
• LH & its analgue
HCG
 HCG
• placental protein that supports corpus luteum
during early stage of pregnancy nearly
identical with LH; its actions are mediated
through LH receptors.
• HCG purified from human urine or
Recombinant form of HCG is used for LH
activity
 Menotropins
• The first commercial gonadotropin product
was extracted from the urine of
postmenopausal women, which contains a
substance with FSH-like properties and an LH-
like substance.
• This purified extract of FSH and LH is known as
menotropins, or human menopausal
gonadotropins
 FSH and its analogue
• Three forms of purified FSH are available.
• Urofollitropin, also known as uFSH, is a purified
preparation of human FSH that is extracted
from the urine of postmenopausal women.
• Two recombinant forms of FSH (rFSH) are also
available:
• Follitropin alpha
• Follitropin beta.
 MOA
• The gonadotropins and HCG exert their effects
through G protein-coupled receptors.
• LH and FSH have complex effects on
reproductive tissues in both sexes.
 Therapeutic uses
• Ovulation induction
• Male infertility due to hypogonadism
 Adverse effects
• In females:
• Ovarian hyper stimulation syndrome
enlarged ovaries, ascites,
Hydrothorax & hypovolemia
• Multiple pregnancies
• In Males:
• Gynecomastia in males
• Headache , depression, edema in both sexes
 GnRH agonist & its analogue
• Gonadorelin ( synthetic human GnRH).
• Synthetic analogs include
• Goserelin,
• Histrelin,
• Leuprolide,
• Nafarelin,
• Triptorelin.
 MOA
• In the pharmacologic use of GnRH continuous
administration of gonadorelin or its longer-
acting analogs produces a biphasic response.
• During the first 7–10 days, an agonist effect
results in increased concentrations of gonadal
hormones in males and females; referred to as
a flare.
• After this period, the continued presence of
GnRH results in an inhibitory action that
manifests as a drop in the concentration of
gonadotropins and gonadal steroids.
• The inhibitory action:
• due to a combination of receptor down-
regulation
• changes in the signaling pathways activated by
GnRH.
 Therapeutic uses
• Controlled ovarian hyperstimulation
• Central Precocious puberty
• Ovarian suppression
• Advanced Prostatic cancer
 Adverse Effects
• In women, continuous treatment with a GnRH
agonist causes the typical symptoms (hot
flushes, sweats, headache).
• Long-term treatment is associated with risk of
bone loss and osteoporosis.
• In men treated continuously with a GnRH
agonist causes , sweats, gynecomastia,
decreased sperm count,decreased hematocrit,
and reduced bone density
 GnrH & their antagonist
• Ganirelix
• Cetrorelix are GnRH antagonists that can be
used during ovulation induction in place of
GnRH agonists to suppress endogenous
gonadotropin production
• Abarelix and degarelix
• GnRH antagonists that are approved for the
treatment of advanced prostate cancer
 Adverse Effects
• similar to those associated with continuous
treatment with a GnRH agonist except that
• they do not cause a tumor flare-up when
used for treatment of advanced prostate
cancer and they may be
• Less likely to cause the ovarian
hyperstimulation syndrome when used for
ovulation induction
 RECEPTOR INHIBITORS

• FLUTAMIDE(competitive inhibitor of androgen

at target cells, ( Prostatic Carcinoma)
• Bicalutamide, Nilutamide ( Orally active )
Leuprolide and Flutamide combination

• Leuprolide ( agonist ) given in continuous

manner along with Flutamide to prevent
tumor flare that can result from surge in
testosterone synthesis caused by initial
agonistic action of GnRH agonist