HORMONAL CONTRACEPTIVES

Dr. SHARON .D.
SHEREGAR MBBS, MD
(Pharmacology)

 Interception in the birth process at any
stage ranging from ovulation to ovum
implantation.
 It includes all measures temporary or
permanent designed to prevent
pregnancy due to coital act.

1) To bring down population growth
2) To reduce infant and maternal mortality
rate
3) To prevent pregnancies that are too
early, too frequent and too many.

First orally active
synthetic steroidal
estrogen was
synthesized in 1938 by
Hans Herloff &
Walter Hohlweg
Ethinyl estradiol &
Mestranol

 In 1950,Pincus,Garcia
and Rock found
progesterone and 19-
norprogestin to prevent
ovulation in women.

 100% effective
 Safe
 Totally reversible
 Acceptable
 Inexpensive
 Simple to use
 Requires minimal motivation, supervision &
maintenance.

Methods of Contraception
c
Natural
Oral
cc
Injectables
Gossypol
Oral
Injectables
Implants
Transdermal patch
Barrier
Permanent
Barrier
Natural
Oral
Permanent

1.NATURAL METHODS
2.BARRIER METHODS
3.INTRAUTERINE DEVICES
4.PERMANENT

Oral Parenteral Devices
1.COC’s 1.Injectables 1.IUD
 Monophasic -DMPA -LNG-IUS
 Biphasic -NET-EN 2.Vaginal Ring
 Triphasic -Combined
2.Minipill 2.Implant
3.Emergency/Post -Norplant
Coital C. -Implanon
4.Centchroman 3.Transdermal patch

1) Combination pills:
A. Monophasic
B. Biphasic
C. Triphasic
2) Minipill / Progestin only pill
3) Post coital / Emergency contraception / Morning
after pill
4) Centchroman

Estrogen (E)
1. Ethinyl estradiol - most common, Dose -0.02 to 0.05mg
2. Mestranol
Progesterone (P)
 19-nortestoterones:
1. Levonorgestrel 0.15 mg
2. Norethindrone 0.5 mg
3. Norgestimate 0.25 mg
4. Drosperinone
Less Androgenic - Norgestimate,Desogestrel, Gestodene

MALA-N
Estrogen (mg) Progestin (mg)
Ethinyl estradiol 0.03 Norgestrel 0.30
Mala-D Ethinyl estradiol 0.03 D-Norgestrel 0.30
Ovral-28 Ethinyl estradiol 0.05 D, L-Norgestrel 0.5
Ovcon 50 Ethinyl estradiol 0.05 Norethindrone 1.0
Norinyl 1/50,
Ortho-Novum 1/50
Mestranol 0.05 Norethindrone 1.0
Femilon 150ug desogestrel +
20ug EE
Loette 100ug LNG + 20ug
EE

B. Biphasic pills: They deliver the same amount of
estrogen each day but level of progestin is increased
about halfway through cycle
Estrogen (mg) Progestin (mg)
Ortho-novum 10/11 , Necon 10/11.
Day 1 – 10 Ethinyl estradiol
0.035
Norethindrone
0.5mg
Day 11 -
21
Ethinyl estradiol
0.035
Norethindrone
1.0mg
Mircette which is biphasic,
changes progeterone
hormone levels twice during
the 28 day pack.

C. Triphasic Tablets: Contain high dose of Estrogen in
midcycle with increasing doses of Progestin given over
3 successive phases.
Attempts to mimic the natural female cycle.
DAYS ESTROGEN PROGESTERONE
1-6 Ethinylestradiol-
30microgm
Norgestrel-
0.05mg
7-11 Ethinylestradiol-
40microgm
Norgestrel-
0.075mg
12-21 Ethinylestradiol
30microgram
Norgestrel-
0.125mg

Category 1: (no restriction of use)
1. Menarche to <40yrs
2. Postpartum >21 days, Post-
abortion
3. Endometriosis, fibroid
4. Iron deficiency anemia

1. Age over40
2. Obesity
3. Migraine
4. Valvular heart disease
5. Diabetes
6. Hyperlipidaemias

1. Cigarettes smoking <15/ day in>35
years
2. Postpartum <21 days
3. Cholestatic jaundice
4. Hypertriglyceridemia

1. Stroke & CAD
2. Hypertension( SBP>160 & DBP> !00)
3. Thrombotic patients
4. Suspected pregnancy
5. Breast cancer
6. Hypersensitivity to any component of pill

 The first pill is taken on 5th day
after start of menses, thereafter,
one pill is to be taken
consecutively for 21days.The next
7 days are Pill Free Period’ & next
course starts after 5th day of
menses.

20
Seasonale Seasonique Lybrel
Aim
• To reduce or even eliminate monthly periods and
thereby prevent the pain and discomfort that often
accompanies menstruation.
• These oral contraceptives contain a combination of
estradiol and levonorgestrel.

21
SEASONALE
 Got approved in 2003.
 It contains 81 days of active pills followed by 7 days of
inactive pills.
 Women who take Seasonale have on average a period
every 3 months.
SEASONIQUE
 84 days of levonorgestrol-estradiol pills followed by 7 days
of pills that contain only low-dose estradiol

22
 Approved by FDA In 2007
 It supplies a daily low dose of
levonorgestrol and estradiol taken 365
days a year.
 It completely eliminates monthly
menstrual periods.

▫ Prevent ovulation by
inhibiting Gonadotropin
secretion via pituitary &
hypothalamic inhibition
▫ Progestational agent in pill ;
suppresses LH secretion
▫ Estrogenic agent ;
suppresses FSH secretion
Failure rate: 0.5-1HWY
23
Hypothalamus
Anterior
pituitary
LH FSH
Estrogen,
Progesterone
GnRH
LH, FSH

Progesterone also:
1. thickens cervical mucus and
2. Prevents passage of sperm into the uterus
3. Changes uterine lining to inhibit implantation
4. Alters secretion & peristalsis within fallopian tubes

Contraceptive NonContraceptive
To Prevent Pregnancy

 Improvement in menstrual abnormalities:
1. Cycle stabilization
2. Reduction of Dysmenorrhea, Menorrhagia
3. Reduction of Premenstrual Tension Syndrome
4. Protection against Iron Deficiency Anemia
 Protection against cancer:
 Endometrial and Ovarian cancer: reduces risk by 40%
 Protection against health diseases:
1. Pelvic Inflammatory Disease
2. Endometriosis
3. Fibroid Uterus
4. Hirsutism and acne
5. Benign breast diseases

Estrogen excess
 Breast tenderness
 Nausea, vomiting
 Chloasma
 Lactation suppression
 headaches
 Gall stones
 Hypertension
 Arterial & venous
thrombosis
 Glucose intolerance
Progestin excess
 Breast
engorgement
 Acne, oily skin,
hirsutism
 Weight gain
 Mood swings
 Increase LDL &
decrease HDL

 They may be Mild, Moderate or Severe.
 Severe A/E require cessation of therapy .
Mild Adverse Effects include:
1) Nausea , breast tenderness, breakthrough bleeding
2) Headache: Often mild and transient
3) Worsening of Migraine / onset of migraine may be
associated with cerebrovascular accidents.
4) Failure of withdrawal bleeding
Change in the preparation or method of contraception.

Moderate Adverse Effects: May require
discontinuation of therapy
1) Break through bleeding
2) Changes in serum lipids :Progestin HDL,  LDL ,
Estrogens:  HDL,  LDL.
3) Weight gain
4)  Skin Pigmentation & Hirsutism; with androgenic
progestin.
5) Acne :  with androgenic progestin,
improvement with estrogenic prep.
6) Vaginal infections
7) Amenorrhea.

Severe Adverse Effects:
1. Vascular Effects:
 Venous Thromboembolic disease: DVT & Pulm
Embolism
 Hypertension
 Myocardial Infarction
 Cerebrovascular disease
2. Depression
3. Gastrointesinal Disorders
4. Others: Alopecia, Skin disorders like
Erythema multiforme, Erythema nodosum .

1. Anti-convulsants: barbiturates,
carbamazepine,felbamate, phenobarbital,
phenytoin, primidone,topiramate, vigabatrin
2. Anti-fungal: Greisofulvin
3. Anti-TB: Rifampicin
4. Antibiotics: ampicillin, amoxycillin,
neomycin, nitrofurantoin, metronidazole,
penicillin, chloramphenicol, tetracycline,
sulfonamide, quinolones.

1. Analogue of spironolactone
2. Good cycle control
3. Progestogenic activity suppress LH
4. Anti-androgenic activity- beneficial
in acne, seborrhoea & hirsutism

1. Progestin with anti-androgenic
property & weak glucocorticoid
effect
2. Useful in Poly cystic ovarian
syndrome (PCOS) & Acne

Levonorgestrel 30 μg, norethisterone 350
μg, norgestrel 75 μg.Desogestrel (75 μg)-
containing minipill (Cerazette®)
POP’s must be taken at the same time
every day.
Good Candidate-
Breastfeeding Woman

Lower dose of progesterone
then OCPs
MOA-
1.Thinning of the endometrial
lining
2.Thickening of the cervical
mucus
3.Slowing ovum transport
through ed tubal motility
4.Inhibition of Ovulation
Absolute C/I
1.Pregnancy
2.Breast cancer
PROGESTIN ONLY MINIPILL
A/E:
The most common A/E
is Episodes of
unpredictable
spotting &
breakthrough
bleeding
.

WHO (1998)
Emergency contraception
can be provided using
1. Emergency contraceptive pills
(ECPs)
Use within 72 hours
2. Intra-uterine devices (IUDs)
Inserted within 5 days and used
as long term method

39
Mechanism of Action:
 Ovulation inhibited or delayed
 Alterations in endometrial receptivity
for implantation
 Dislodges an implanted Blastocyst.
 Production of cervical mucus that
decreases sperm penetration
 Alterations in tubular transport of
sperm, egg or embryo

1. Yuzpe regimen:
a) 2 doses of COCPs containing EE
50µg& levonorgestrel250µg-in 72hrs
&next after 12hrs.
b) Effective-90%
2. 2 doses of levonorgestrel 0.75mg each-
1st in 48hrs & 2nd in 12hrs.
EC2, Pill 72, E-Pill, Norlevo, i pill
(available in India)
3. Mifepristone: 600 mg once in 72 hrs.
40

41
Recently approved in 2010,
ULIPRISTAL ACETATE (SPRM) in
a single oral dose of 30mg is more
effective if taken in 120hrs/5days.
If these measures fail, pregnancy
should be terminated to avoid
teratogenic deformities of fetus.

42
 SERM, non-steroidal
 Once per week, 30 mg
 First 3 months - pill twice per week
 Later followed by once per week
 Also for treatment for DUB
 Saheli, Centron & Sevista
Mechanism of action
• Asynchrony between ovulation &
development of uterine lining
• Speeds transport of egg through
fallopian tubes
• Implantation not possible
Pearl Index - 9

43
Progesterone only injectables:
• Intramuscular injection
DMPA: 150 mg every 3 months
300 mg every 6 months
NET-EN: 200 mg every 2 months
Failure rates: DMPA: 0.1/HWY
NET-EN: 0.4/HWY
1992,FDA
approved

44
 FDA approval 2004
 Sustained absorption of progestin
 Low dose of progestin (104 mg instead of 150 mg)
 Injections every 3 months
Mechanism of action:
1. Inhibits ovulation
2. Thick cervical mucus

45
COMBINED INJECTABLES-Given at
monthly intervals-IM
• 1.Estradiol valerate5mg+17-hydroxyprogesterone
caproate250mg
• 2.Cyclofem/Cycloprovera/Lunelle(DMPA25mg+Estra
diol cypionate5mg)Failure rate: 0.2 %
• 3.Mesigyna (NET-EN + Estradiol
valerate)FailureR:0.4%
Mechanism of action
1. Suppresses ovulation
2. Thickening of cervical mucus
3. Reduced receptivity of endometrium to blastocyst

1. Single flexible rod 4 cm
long, contains 68mg of
etonogestrel
2. Releases 60 µg/day for
3 yrs
3. Inhibits ovulation within
8 hrs of insertion &
provides contraception
for 3 years
Uniplant: contains 55 mg nomegestrel acetate in
a 4cm silicone capsule with 100ug release per day
IMPLANTS: IMPLANON

Each rod measures 2.5
mm in diameter & 4.3 cm
in length containing 75
mg of LNG
Drawbacks IMPLANTS-
Irregular bleeding
Spotting
Amenorrhoea
Occasional removal problems
Failure rate: 0.1/HWY

 Inserted at any time
during menstrual cycle
 Sub-dermally on the
inner aspect of the non-
dominant arm
 Removal requires
making 2 mm incision
at distal tip of implant

Works trans-dermally by:
1. Combination of progestin & estrogen
2. Slowly releasing
3. Through skin
Types:-
1. Patch
2. Spray-on
3. Gel
49

 Transdermal contraceptive patch
‘OrthoEvra’ was approved by US FDA in 1992.
 Sites:
Buttocks, Upper outer arm
Lower abdomen, back,
upper torso.

 3-patch system
 Apply 1 patch each week for 3 weeks
 Apply each patch the same day of the week
 1 week is patch-free
Week 1 Week 2 Week 3 Week 4
Patch #1 Patch #2 Patch #3
28-day cycle
Patch-free
Week 5
Start next cycle
28-day cycle

 Nestorone - Metered Dose Transdermal
System (MDTS)
 In phase I trial as of Feb 2009
 Absorbed instantaneously
 MDTS® daily skin spray formulations
 Hormone collects as reservoir with in
the skin and slowly diffuses into the
blood stream

First generation
• Inert, non
medicated
• Polyethylene/o
ther polymers
Second
generation
• Addition of
metallic
copper
• Cu- anti
fertility effect
• Smaller
devices, easier
to fit
Third generation
• Hormone
releasers
Intra-Uterine Devices

• Third generation: Hormone
releasers
1. Progestasert – 38 mg progesterone
2. Mirena/LNG IUD:
- Effective life of 5 yrs
- 52 mg of levonorgeterel
3. Fibroplant
 LNG released@14ug/day
 Suitable in peri-menopausal women.
 Effective for 3 years.
54

 Expulsion
 Uterine Perforation
 Irregular bleeding
 Pelvic infection
 Ectopic pregnancy
 Pain
 Pregnancy: Failure rate in 1st year- 3%

The first vaginal contraceptive ring ‘NuvaRing’
was approved by FDA in 2001 & marketed in
2002
• Releases 15ug EE &
120ug etonogestrel
over 24hrs

 Soft polymer device
NuvaRing:
 Monthly
 Used for 21 days followed by 7 day hormone-
free interval
 Completely inhibits ovulation
 ADRs
 Vaginitis,Leucorrhoea,Headache,Expulsion
57
Failure rate: 1-2/HWY
54 mm
4 mm
Vaginal ring

 Non-steroidal
 Derived from cotton seed
and used in China.
 Dose: 20mg/day for initial
2-3 months followed by
50-60 mg/week for not
more than 2 yrs.
 Mechanism Of Action:
Decreases sperm count and
sperm motility. 61

Vasectomy
Tubal occlusion/Tubectomy
Hysterectomy
Laparotomy/Mini lap

63
 Desogestrel : Approved in 1998, Mircette was the first
oral contraceptive to offer a low estrogen dose and a new
type of dosing regimen. Some studies suggest an increased
risk for blood clots with desogesterel.
 Levonorgestrel : is used in Seasonale and Seasonique,
as well as many other oral & non-oral contraceptives.

64
86% success rate for 1st time
placements of micro-inserts
3 months of alternative
contraception
Follow up HSG procedure

65
EssureTM Micro-Insert
(Approved in 2002)

66
 Monolithic microspheres
 Steroid esters
 Microspheres
 Immuno-contraceptions
 Sperm and Ovum Immuno-contraceptives.

67
HCG IMMUNOCONTRACEPTIVES
• The most advanced immuno-contraceptives are those
based on hCG.
• Three main types have been developed:
1. hCG-beta subunit conjugated to tetanus toxoid (hCG-TT)
2. hCG beta subunit - ovine LH alpha subunit conjugated to tetanus
toxoid and diphtheria toxoid (HSD-TT-DT)
3. hCG beta subunit C-terminal 37 residue conjugated to diphtheria
toxoid (CTP-DT).

HORMONAL CONTRACEPTIVES

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