Anti Fertility Agents and

Ovulation Inducing Drugs

Submitted By
P.Poongothai
Physiology of Human Reproduction
The reproductive cycle in the human in when
Ovulation is a key event. is the result of the
interplay of the hypothalamus the pituitary and the
ovaries. With respect to ovulation, the mammalian
females can be divided into two groups
I.Relfex ovulators
E.G.Rabbits, Cats, ferrets and rinks, in when the
sensory stimulus of mating or electrical stimulation
of cervix induces ovulation.
II.Spantaneous ovulators
like cows, monkeys and women in whom to
follicular rupture occurs in the absence of any
immediate sensory stimulus.

Fertility Control
The Fertility control can be achieved by
Controlling the central mechanism
Modifying other physiological mechanism of
reproduction
Preventing the union of sperm with ovum

Fertility Controlled by using drugs which can act by
Inhibiting ovulation
Modifying the cervical mucus
Interfering with the implantation
Slowing down the rate of egg transfer
Preventing the ovum maturation and sperm
capacitation
Immunological methods : and
Inhibiting spermatogenesis in males

Estrogen progestin combination pill
Since the first clinical demonstration of use3fulness
of such an oral combination for contraception by
pincus (1955) Several commercial preparations
have been available. The pills are
Remarkable efficacy
Relative safety; and
Ease of administration

Combination oral contraceptive (COC) pills :
It contain
a) Ethinylestradial or its 3-methyl either mestranol
as the estrogen; and
b) A progestin belonging to 19-nortesterone group
(nonethisterone, norgestral or ethynodiol
acetate) or a derivative of norgestrel
(desogestrel)

Methods of Administration
Fixed dose combination pills (Monophasic pills)

The commonest procedure is to administer
one pill containing both an estrogen and progestin
daily, orally at bed time, for 21 days, from 5
th
to
25
th
day of 28 day cycle. The next coarse is started
7 days after the last dose.

The pill should be avoided in breast feeding
women as if interfers with lactation

When used properly the Pill is the most effective
(99% to 100%) contraceptive available.
Biophasic and Triphasic combination pills :
These are combination oral contraceptive pills
containing varying proportions of an estrogen
and a progestin and are designed to stimulate
the hormonal profile of the normal menstrual
cycle.

Extended cycle COC :

a) A COC pill containing 30 mcg of ethinyl estradiol
and 150 mcg of levonorgestrel (seasonable) if
taken daily for 84 days. The major advantage is
it reduces the number of menses.
b) Another pill available (Lybrel) contains EE 20mcg
and levonorgestrel 90 mcg. It cause
amenorrhaea within an year.

Mechanism of action
The mechanism of the contraceptive action of these
agents in complete, The combination type suppresses both
FSH rise (due to the estrogen component) and LH peak (due
to the progestin component) observed during the normal
menstrual cycle by inhibiting the release of GnRH. Thus
follicular growth is not initiated and ovulation does not
occur.
Pharmacological actions of COC pills
Endometrium
Pituitary ovarian axis
Metabolic effects
Hyperglycemia
Glycosuria
Mildly impaired glucose tolerance
Abnormal GTC related to dose to progestin
Desogestrel affect carbohydrate metabolism
Cholesterol increase
LOL Increase
HDL Decrease


General
Nausea
Ancrexia
Vomiting

Bleeding irregularities
Thromboembolic phenomena
Hypertension
Uterine fibroids
Carcinogenicity
Therapeutic use
An oral contraceptives
These pills safe, lighty effective and acceptable
Postcoital contraception
Polycystic contraception
Dysfunctional uterine bleeding
Premature menopause
Turner syndrome
Progestins Alone as contraceptives
Levonorgestral

This 19, nortestosterone compound possess
very potent progestational activity. In the daily and
dose of 30mcg (Microval) continuously. If prevents
conception. The drug probably acts by several
mechanisms. It reduces the sperm penetrability of
the cervical mucus and impairs luteal function. It
causes irregular and generally start bleeding
intervals.

Progestin-only pills are currently used an
only in patients with a specific contraindication to
estrogen, in breast-feeding mother. The pill should
be started by a breast-feeding mother 6 weeks
after childbirth.
Antiestrogenic Agents
Levormeloxifene

This chroman derivative, shows weak
estrogenicity, potent anti-estrogenicity and is
devoid of progestogenic or androgenic activity.

The main side effect is prolonged menstrual
cycle, and enlarged ovaries. It should be avoided in
polycystic ovarian disease, renal and hepatic
disorders, tuberculosis and lactating mothers.
Injectable contraceptives

Injectable progestational preparations,
depotmedrooxy progestrone acetate and
norestisterone enanthate are highly effective, long
active. They enter circulation directly with out
passing through liver. They dont cause birth defect
and not affect sex drive.

Medroxyprogestrone Acetate
MPA is a progestational compound which is
effective both orally and parenterally. It is not
metabolized into estrogen in body. The long acting
DPMA is given by IM and inhibit LH, lead to
suppression of valuation. It act on endometrium
fallopian tube and cervical mucus and excrete in
breast milk but does not suppress lactation.
Repeated injections cause prolonged ovulation
inhibition for several months after discontinuation.
Adverse Reactions

Bleeding irregularities, spotting, prolonged
amenorrhea, weight gain and adrenal suppression.

Levonorgestral Implant
It consists six, flexible, silastic rods,
containing levonogestral in crystalline form. The
machanism of action of this is an antiestrogenic
on endometrium and cervical mucus which become
thick and adverse to sperm penetration. LH peak
and ovulation are suppressed.

Adverse Reactions

Local injection, irregular bleeding,
amenorrhoea, headache, nervousness, nausea,
skin rash, aone, hirustism, brest tenderness,
weight gain and enlarged ovarian follicles.

Progestin IUCD
progestasert consists of progesterone micro-
crystals in a silicon fluid, surrounded by a release-
rate-limiting membrane. It release minute
quantities of drug over a period of one year.
Menstrual pattern is not disturbed, ovulation is not
suppressed and it used to treat menorrhagia.

Mifepristone (Ru 486):
This derivative of norethisterone has antiprogestin activity.

Pharmacological actions:
Administered to women in early and late luteal phases of the
menstrual cycle. It inhibit glandular secretary activity and accelarate
degenarative vascular changes lead to menstrual bleeding within 72-
hours. It acts as progesterone antagonist in the presence of.
Progesterone and act as an agonist in the absence of progesterone.

Absorption, Fate, Excretion
It administered :orally or parenterally and metabolized slowly
by liver and excreted in bile.

Adverse reactions:
Single dose cause nausea vomitting, abdominal pain, and
heavy prolonged bleeding. Long term administration cause fatigue,
anemia, weight loss, thining of hair, menstrual disturbance, decrease
in libido and gyneco mastia.




Therapeutic uses:
Post coital containing IUCDS inserted within 5
days from the day of sexual inter course is also
effective as post. coital contraceptive agents.
Induction of abortion.
Cervical dilatation.



Male contraception:
In males androgen, estrogen, progestin and also
steroid combination inhibit spermatogenesis.
Gossypol:
It is a polyphenolic compound obtained from cotton
seed. In rat, it cause dose dependent germinal cell
damage of testes, long term treatment lead to
sterility. It does not damage leyding cell and no
genetic damage. Adverse effects are GI
disturbances, fatigue, dizziness, decreas3ed libido,
hypokalemic paralysis.

Ovulation Inducing Drugs:
The problem of infertility is a joint one and both
partners need detailed examination.
Deficiency of the thyroid hormone is an
uncommon cash cause responsible for anovulatory
cycles. Estrogen administration cause LH release in
rodents, monkey and women. Low dose estrogen
use in some follicular activity is present but
midcycle LH peak is lacking or corpus luteum is
inadequate.
Progestins are useful in inadequate corpus
lueteum and endometriosis.
Dexamethasone in small doses (0.25 0.5
daily) induces ovulation in some PCOs patient by
suppressing androgen



Classification of ovulation inducing drugs

I. Synthetic GnRH
II. Human manopausal and chorionic
gonadotrophins
III.Bromergocriptine
IV. Anti estrogenic compound clomiphene citrate



Clomiphene Citrate

It is a triphenylesthylene compound resemble
to stilbestrol and chlorotrianisene. In rat, it
stop estrous cycle, decrease secretion of
gonadotropins and reduce the size of ovaries. It
induce ovulation. It available in Cis and trans
form and cis form structurally resembles to
estrogen

Pharmacological actions
Antiestrogenic action
It bind to estrogen receptor result in
estrogen antagonist action.

Miscellaneous action
It has a weak estrogenic action, on bone
and endometrium.

Absorption, Fate and excretion
It given orally absorbed in intestine and
excreted in feces and small amount in urine.

Adverse reaction
Hot flushes
Ovarian enlargement
Multiple ovulation

Therapeutic uses
Ovulation induction
Polycystic ovary syndrome
Oligospermia


Cylclofenil
It structure similar to clomiphene and
used to similar purpose. It given 200mg
twice a day for 10 days, it induce
ovulation.
Letrozol
This aromatase inhibitor used for
ovulation induction in PCO patients. It
reduce estrogen. It promote the
development of healthy ovarian follicles
and ovulation.

Thankyou