Contraceptive
326
Dr.Hazar
Objectives
List the drugs and mechanisms used to attenuate
the actions of sex hormones.
Ex. Gonadotrophines releasing hormones ;agonists
&antagonists.
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Understand the Types ,MOA,S.E ,uses & C.I. of
the hormonal contraceptive drugs.
Understand the Types ,MOA,S.E ,uses & C.I. of
the fertility drugs.
Gonadotrophines releasing hormones
agonists &antagonists.
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1.danazol &danazol analogues
2.gonadorelines analogues
3.fertility drugs
1.danazol &danazol analogues
Danazol
1.Gonadotropin inhibitor with antiestrogen
,progestational and androgenic properties
2.synthetic version of the male hormone testosterone
3.inhibits the release of FSH and LH by the pituitary
gland
4.decreases estrogen levels similar to menopause,
stops ovulation
5.shrink abnormal implants
Danazol

Indications:
1.Endometriosis
2. Mammary dysplasia (fibrocystic breast
nodularity)
3. Menorrhagia ;(but not contraception).
4.Gynaecomastia.
Danazol
Side effects
 androgenic effects (deepening of the voice,
abnormal hair growth, reduced breast size,
water retention, acne, weight gain ;nearly
all gain weight between 8-10 lbs.)
 hypoestrogenic reactions (flushing,
sweating, vaginal dryness, irritation)
 amenorrhea
 irregular vaginal bleeding, muscle cramps
Danazol analogues
1-Gestrinone is danazol agonist
Ditto action –danazol
Used only in Endometriosis
2-Cetrorelix-LHRH antagonist ↓FSH &LH
used in infertility.
3-Ganirelix-ditto
2.Gonadorelines analogues
Continuos use
1. ↓ Gonadotropines Receptors and
sensitivity in the Pituitary ; Down
regulation
2. ↓ LH,FSH ;estrogen level ↓
3. No ovulation
4. ↓ endometrium
Treatment
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Endometriosis
Polycystic ovarian Disease
Prostate Cancer
Precocious Puberty
Breast Cancer
2.Gonadorelines analogues
Pulsatile use
1.
Activation of natural Gonadotropines
pituitary Receptors to stimulate release of
FSH and LH
Indication
Induction of ovulation invitro fertilization
Types of Gonadorelines
analogues
GnRH Analogues
Nafarelin
-nasal spray approved in 1990
-200x>potent than natural LHRH
-relieves symptoms and shrinks implant or stops -them from
growing
-puts body into menopausal like state
-side effects:
hot flashes; vaginal dryness; lighter, less
frequentor no menstruation; headaches; nasal irritation
-should not be used in women who are pregnant, breast
feeding, or have undiagnosed vaginal bleeding
Goserelin
·
·
·
Made specifically for treatment of
endometriosis in 1990
by decreasing the amount of estrogen in the
body, the body is induced into a menopausal
state
may be administered by a subcutaneous
implant which is placed in the abdominal
wall
Types of GnRH analogues+uses
Types
Endometriosis Prostate cancer
IVF
Buserelin
+
+
Nafarelin
+
+
Leuprolin +
+
Triptorolin
+
+
Goserelin +
+
+
Breast cancer
+
Contraceptives
Objectives
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1. Understand the mechanisms by which oral
contraceptives prevent ovulation.
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2. Know the potential adverse effects & containdication of
oral contraceptive therapy .
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3. Become familiar with the other type of contrceptives
( non oral )
REF
1. Katzung's.
2. Rang & Dale
3. Goodman and Gilman
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Types of Oral Contraceptives
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Types of preparations
 1. Combinations - contain an estrogen and a
progestin given continuously for three weeks
(most widely used).
 a. High dose estrogen ≥ 0.05 mg (first
generation)
 b. Low dose estrogen < 0.05 mg, usually
0.02 - 0.035 (second generation)
 c. Low dose estrogen with a lesser
androgenic progestin (third generation)
2.Sequential Products
a. monophasic
b. biphasic
c. triphasic
Monophasic OC
3. Minipills-progestin only (block ovulation,
slowing GnRH pulse generation 
decreased LH surge)
For female with:
Venous thromboembolism , smoker, DM, HT,
migrain & lactation.
4. Morning-After Pill (administer within 72 hrs
of coitus, continue 2x for 5 days)
Emergency contraceptives

drugs used for the prevention of pregnancy following
unprotected intercourse or a known or suspected
contraceptive failure
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to be effective these must be taken within 72 hours of
intercourse
two products are available:
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Plan B: 0.75 mg levonorgestrel
Preven: 0.25 mg levonorgestrel and 0.05 mg ethinyl estradiol (this product
includes a pregnancy test kit)
Mechanism of Action
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Combination
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Inhibition of ovulation via continuous negative feedback on
hypothalamic-hypophyseal axis (LH/FSH suppressed, no
LH surge)
Progesterone decreases the frequency of GnRH pulses
Changes in the Endometrium
Thickens cervical mucus- difficult sperm penetration
Changes in the Fallopian Tube
Prevent follicular maturation
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M.O.A Progestins alone
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1.There is variable suppression of FSH, LH and ovulation.
Menstruation may occur with irregular cycles.
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2. Altered endometrial structure may prevent implantation and
heavy cervical mucus may prevent sperm penetration.
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3. Continuous use lends itself to long-acting preparations intramuscular, subcutaneous, or intrauterine depots
(medroxyprogesterone acetate, levonorgestrel).
Names
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Combinations
Estrogens: Ethinyl estradiol ,Mestranol
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Progestins : levonorgestrel , Norethindrone
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Progestins-only
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Levonorgestrel , norethindrone, ethynodiol
diacetate
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Morning-After
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Diethylstilbestrol
Norethindrone
Ethinyl estradiol + levonorgestrel
Postcoital IUD contain Cu (best)
Other oral preparations:
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Ethinyl estradiol + norethindrone
Ethinyl estradiol + ethynodiol diacetate
Ethinyl estradiol + norethynodrel
Ethinyl estradiol + levonorgestrel
Adverse effects
Estrogen-related
1.Cardiovcascular Disease
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a. Deep vein thrombosis
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b. Thromboembolism
Thromboembolic disorders due to effects on
clotting factors and platelet aggregation
properties; myocardial infarction; stroke
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Nausea, vomiting
Edema (weight gain, breast engorgement) due to salt and
water retention
Headaches, dizziness
Hypertension resulting from salt and water retention and
increased hepatic secretion of angiotensinogen
Breakthrough bleeding
Urinary tract infection
Folic acid deficiency
Increased serum triglycerides
Dysmennorrhea
Ocular changes
Chloasma
Gall bladder disease related to increased cholesterol
precipitation due to a decrease in bile flow
• Decreased glucose tolerance via lowered sensitivity
to insulin; possibly related to estrogen-stimulated
release of insulin-antagonistic hormones (e.g., GH,
T3+4, cortisol).
• Carcinogenesis
a. breast
b. endometrial
c. ovarian
d. cervical
e. hepatic
Progestin-related
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Depression - possibly related to increased
MAO activity
Headaches
Loss of hair and/or hirsutism, acneassociated with 19-norsteroids
Yeast infections
Contraindications to Oral Contraceptive Use
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Current or past history of deep vein
thrombosis, stroke, coronary artery disease,
or hypertension
Cancer of the breast
Strong family history of the above
Active liver disease
Heavy cigarette smoking Stroke - smokers
over 35
Types of non oral contrceptives
1.Barrier-condom
2.Devices-IUD – (levonorgestrel,Cu),Cap.
3.Spermicidal-Nonoxinol (creams and gels).
4.Injections
Monthly injectable – medroxyprogesterone1/12
Norethisterone 8/52
5.Vaginal ring - ethinyl estradiol + etonorgestrel
6.Patch - ethinyl estradiol + norelgestromin
7. Levonorgestrel implants .
Levonorgestrel Intrauterine
Device
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Releases 20 µg levonorgestrel each day
Indicated for contraception
80%–90% reduction in menstrual blood loss (not
associated with copper-T IUD)
Also effective in treating menorrhagia, endometriosis
Use up to 5 years
Side effects: breakthrough bleeding, ovarian cysts,
acne
Cost effective
Levonorgestrel-releasing intra uterine system
Progesterone releasing IUD
Superior to oral progesterones reduces MBL by 96%
64% women cancelled hysterectomy compared to 14% on
medical treatment, effective contraceptive
Suppresses development of endometrium but does not
suppress ovulation
Effective for 5 years
90% women menorrhagia cured in 3 months
Infertility
Ovulatory Dysfunction
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Causes of ovulatory dysfunction:
polycystic ovary syndrome
 hypothalamic anovulation
 hyperprolactinemia
 premature and age-related ovarian failure
 luteal phase defect
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Polycystic Ovarian Syndrome
Oligomenorrhea/amenorrhea and
hyperandrogenism
 Prevalence: 5%. Among women with O.D.,
70% have PCOS.
 Clinical evidence: hirsutism, acne, obesity
 Lab evidence: elevated testosterone, elevated
DHEA-S.
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PCOS: Treatment Approach
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Weight loss if BMI>30
Clomiphene to induce ovulation
If DHEA-S >2, clomiphene + glucocorticoid
(dexamethasone)
If clomiphene alone unsuccessful, try metformin +
clomiphene.
Endometriosis Medical
Treatments
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Oral Contraceptives
Progestins
Danazol D.O.C
NSAIDs
GnRH analogues