Hormonal Contraceptives MBBS YEAR 2.PDF.

Pharmacology MBBS Year2 Aimst University

1. Hormonal Contraceptive
Dr. Nazmun Nahar Alam
Asst. Prof. Pharmacology
AIMST University

2. Learning Outcome
At the end of the lecture, students should be able to:
•State the hormonal changes leading to ovulation.
•Classify hormonal contraceptives based on their components.
•Describe the types of combination oral contraceptives.
•Describe the mechanism of action, methods of administration, adverse effects,
contraindications and health benefits of hormonal combination contraceptives.
•Describe the mechanism of action, methods of administration, adverse effects and
advantages of progestogen alone contraceptives.
•Describe drugs for emergency contraception.
•Describe the mechanism of action, uses and adverse effects of clomiphene citrate.
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3. Ovulation& Drugs
•Inhibition –Contraception
•Induction –Treatment of sterility
•Hormonal contraceptives are drugs used to prevent conception
•Hormonal contraceptive “Pill” was introduced in 1960 & became the most commonly
usedmethod of contraception.
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4. Contraception means prevention of pregnancy.
•Hormonal contraceptives
•Non-hormonal methods:
•Barrier method
•IUD
•Methods based on information
•Permanent sterilization
There are several methods of contraception-
Contraception
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5. Hormonal Contraception
❑Hormonal contraceptives are -
▪Oral pills
▪Implants
▪Injectables
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6. Oral contraceptives…
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•Combinations of estrogen & progestins
Combined oral pills:
•Continuous progestins therapy without concomitant administration of
oestrogens
Progesterone only pill:
•postcoital pill
Estrogen containing preparations: e.g.

7. Contents of oral pills
•The estrogen in most combined preparations is ethinylestradiol. A few
preparations contain mestranol.
•The progestogen may be norethisterone, levonorgestrel, ethynodiol,
or
•In 'third-generation' pills-desogestrelor gestodene
•more potent, have less androgenic action and cause less change in
lipoprotein metabolism but
•which probably cause a greater risk of thromboembolism
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8. Physiology of ovulation
•At the beginning of each cycle, vesicular follicles begin to
enlarge in response to FSH
•After 5/6 days, a dominant follicle develop, outer theca & inner
granulosa cells of the follicle multiply.
•Under influence of LH, theca & granulosa cells secret estrogen.
•At midcycle high level of estrogen inhibits FSH & there are
regression of less mature & smaller follicle.
•LH surge with high level of estrogen leads to rupture of mature
ovarian follicle & ovulation occur.
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9. Physiology of ovulation….
•The ovum is released into the abdominal cavity after ovulation,
ruptured follicle is filled with corpus hemorrhagicum & luteinized
theca & granulosa cells begin to secretprogesterone mainly this is
corpus luteum.
•If pregnancy does not occur, corpus luteum degenerates. It becomes
corpus albicans & ceases hormone production
•Fall of hormone level does not support endometrium.
•The endometrium, proliferates during follicular phase. It develops its
glandular function in luteal phase.
•Withdrawal of hormone level leads to shedding of endometrium &
menstruation occurs
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10. Principles for hormonal contraceptives
•Hormonal contraceptives must be extremely safe & highly effective
•Onset of action must be quick & completely reversible
•Ease of use and additional health benefits
•Alternative methods are less reliable & inconvenient
•Reversibility of action
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11. Negative
feedback
Hormonal relationships of the human menstrual cycle.
Pill
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12. Types of Hormonal contraceptives
1.Combination contraceptives–Estrogen + Progestogen
Ovulation is prevented.
•High Efficacy –99.75%
2. Progestogen alone contraceptives/ Progestogen only Pill (POP)–Efficacy -98.8%
•Efficacy slightly lessthan that of combination type as Ovulation is not always
prevented.
•Progestogen alone contraceptive is preferred in women with contraindications to
estrogen.
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13. 1/29/2024 Dr. Nazmun@AIMST

14. Hormonal contraceptives (1) -MOA
Hypothalamic GnRHrelease
GnRHreleases FSH & LH from pituitary
Mid-cycle surge of LH results in ovulation
Estrogen & Progesterone (in the combination contraceptive
pill), through negative feedback, inhibit the release of
gonadotropins, inhibit follicle maturation & prevent ovulation.
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15. Combined pill -Mechanism of action:
•Inhibition of ovulationis the primary mechanismof action.
Estrogen & Progestogen synergisticallythrough negative feedback, inhibit the
release of gonadotropins, inhibit follicle maturation and prevent ovulation.
•Progestogen ↑ the viscosity of cervical mucuswhich becomes impenetrable to
sperms.
•Additional actions: altered endometrium, altered motility of tubes prevent
fertilization & implantation.
Hormonal contraceptives (2) - MOA
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16. 0 4 8 12 16 20 24 28 Progesterone on
Cervical mucus
Menstruation
OVULATIONCervical
mucus
Production
of low
viscosity
mucus
increases
Abundant mucus - like
“raw egg white”
Thick, rubbery, high
viscosity - impenetrable
to sperm.
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17. Types of Combination contraceptives-
Phased Formulations
Based on the ratio of estrogen& progestogen, combination pills are classified
into different phased formulations-
Pills with constant ratio
•Monophasic pills –all 21 pills contain same quantity of estrogenand progestogen .
May be low estrogen/ high estrogen
Pills with variable ratio between estrogen& progestogen –
•Biphasic pills –dosage (quantity per pill) of one or both components changed once
•Triphasic pills –dosage changed twice
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18. Combination contraceptives
The advantages of phase formulations (especially with the triphasic pill)
is to minimise ADR by –
•decreasingthe total quantity of the hormone administered.
•mimicking the natural (body) pattern of cyclic hormone secretion.
•Progestogen is low at the beginning and high at the end.
•Estrogenremains constant or higher slightly at mid-cycle.
To the 21 pills, 7 placebo tablets are added to accommodate the 28 day
cycle.
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19. Combination contraceptives - ADR
Serious ADR are rare & are often seen in women with other predisposing
factors as the present OC are lowestrogen pills.
Mild ADR:
•due to estrogencomponent -Nausea, edema, Breast tenderness.
•Reversible increase in BP, may necessitate stopping of OC.
•Headache, migraine -if migraine becomes worse OC is stopped as
cerebro-vascular accidents (CVA) may occur.
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20. Drug interactions resulting in ‘pill failure’:
•Microsomal enzyme inducers: Antiepileptics, Rifampicin
•Drugs altering enterohepatic circulation: oral antibiotics
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21. Combination contraceptives - ADR
Moderate ADR: breakthrough bleeding, weight gain, acne, skin pigmentation,
hirsuitism, amenorrhea
Severe ADR:
•Due to estrogen -thromboembolism, MI, deep vein thrombosis
•Due to progestogen -depression, increased incidence of cholecystitis, hepatic
adenoma
•Severe ADR due to estrogen are especially more in
smokers,
age >35 yr. &
hypertensive
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22. Combination contraceptives - Contraindications
Absolute Contraindications
•Previous thromboembolic event or stroke
•History of an estrogen-dependent tumor
•Active liver disease
•Pregnancy
•Undiagnosed uterine bleeding
•Hypertriglyceridemia
•Women over the age of 35 years who smoke heavily
Relative Contraindications
•Depression, lactation, migraine, jaundice, HT, DM, obesity
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23. Combination contraceptives
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Additional health benefits of combination
contraceptives
•Menstrual regulation
•Reduced Risk of anemia
•Decreased Risk of ovarian, endometrial & colon cancer
•Less Incidence of pelvic inflammatory disease
•Reduced Incidence of breast disease
➢Missed pill: missed pill to be taken within 12 h & additionally to follow
barrier methods. Preferably, pill should be taken at the same time of
the day.

24. Combination contraceptives –Drug Delivery
Systems
Pills –
•28 pill pack with 21 active pills + 7 placebo tablets
•Extended cycle pack -12 wk(84 day) pack + 7 placebo tablets
Hormonal Contraceptive transdermal patch -
One contraceptive patch each week for 3 weeks & week 4 free.
Hormonal Contraceptive vaginal ring -
Ring for 3 wkand week 4 is free.
Ointmentfor wklyapplication for 3 wk& one week free.
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25. Progestogen only contraceptive pill (POP) (1): “Mini-Pill”
Norethisterone / Levonorgestrel
•Taken continuously daily.
•Efficacy – 98.8%
MOA –
•Alter cervical mucus into a thick tenacious consistency.
•Endometrium unsuitable for implantation.
•Altered motility of uterus, tubes unsuitable for implantation.
•Prevents ovulation in only 60-80% of cases.
ADR/ Disadvantages: breakthrough bleeding, weight gain, other
progestogen effects like increase in BP, decrease in HDL etc.
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26. Progestogen only contraceptive : Mini Pill
“For whom to prescribe “Mini-Pill”? –
To women with contraindications to estrogens such as -
• hepatic disease, hypertension, IHD, prior thromboembolism, psychosis,
migraine, smokers > 35 yr
•during breast feeding
Advantages of Mini pill:
•Does not affect lactation
•↓ incidence of pelvic inflammatory disease.
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27. Progestogen only contraceptive : Injectable
progestins
•Progestins for long duration contraception
•MedroxyProgesterone Acetate (MPA):
•im/ sconce in 3 months
•May prevent ovulation as high plasma levels are achieved &
amenorrhoeaoccurs. As effective as combination OC.
•Menstrual irregularities are commonand infertility may persist for
many months after cessation of treatment.
•May cause osteoporosis. Hence, not to be given for more than 2 yr.
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28. Progestogen only contraceptive - Implants
Etonogestrel implants–subcutaneous implants in the
form of non-biodegradable capsules provide reversible
contraception. Widely used all over the world.
•No 1
st
pass metabolism in liver.
•Do not alter the lipoprotein levels.
•Duration of action –3 yr
ADR:
•Low hormone levels and hence, minimal ADR.
•Irregular menstrual bleeding and headache.
•surgical insertion and local infection
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29. Progestogen only contraceptive
- Other dosage forms
Intrauterine device (IUD) with progestogen
•Levonorgestrel IUD -Acts locally
•duration of action -1 yr/ upto5 yrs
Intravaginal ring with progestogen:
•Levonorgestrel -local action
•Duration of action -3-6 months
•ADR:weight gain, acne, breakthrough
bleeding, amenorrhea
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30. •Prevention of pregnancy as part of ‘Family planning’
–commonest use
•Prevention of pregnancy following failure of barrier
devices, unprotected sex or in emergency such as
rape –The regime is known as ‘Post-coital pill’
(Morning after pill) or ‘Emergency contraception’.
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Hormonal Contraceptives are
used:

31. •Indicated in rape, unprotected sex etc.
•Should be used within 72 hoursof unprotected sex.
•Does not affect established pregnancy.
1.Levonorgestrel,taken ASAP and repeated 12 h later.
Efficacy –99%
MOA:
•Alter endometrium, tubal motility, gamete survival
•Prevent fertilization and implantation.
2.Combined OCP: 2 pills immediately & 2 pills after 12 hours
Nausea & vomiting can occur
Post-coital pill (Morning after pill) / Emergency
Contraceptive
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32. 3.Mifepristone (RU 486)–is an anti-progestogen acting as luteolytic. Given
orally in a single dose ASAP within 5 days of unprotected sex.
Uses:
•Post coital contraceptive.
•Along with either oral or vaginal prostaglandins as a first trimester
abortifacient within 9 weeks of pregnancy.
Ulipristal: selective progesterone receptor modulator –
partial agonist. Effective upto5 days.
Post-coital pill (Morning after pill) /
Emergency Contraceptives
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33. Ovulation
Inducing Agents
•Gonadotropins
•Clomiphene citrate
❑Clomiphene citrate-Partial agonist /
•Competitive antagonist at estrogen receptors.
•↑gonadotropin release by removal of –vefeedback resulting
in ovulation
•Given from 5
th
day for 5 days orally.
ADR:
•hot flushes, multiple pregnancy, ovarian cyst
Uses:
•1. In women to treat infertility
•2. To improve low sperm count in men.
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34. Reference
•Katzung'sBasic and Clinical Pharmacology, 16th Edition (Lange Medical Books) 16th
Edition
•Lippincott Illustrated Reviews: Pharmacology (Lippincott Illustrated Reviews Series)
Eighth, North American Edition by Karen Whalen PharmD BCPS.
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