Contraception

Marwa Adel, PhD

Lecturer of Clinical Pharmacy
Faculty of Pharmacy, Ain Shams University
 LEARNING OBJECTIVES
• Discuss the physiology of the female reproductive system
• State the mechanism of action of hormonal contraceptives
• Discuss risks associated with the use of hormonal contraceptives, and state
absolute and relative contraindications to their use
• List side effects associated with the use of oral hormonal contraceptives, and
recommend strategies for minimizing or eliminating such side effects
The menstrual cycle
 Types of
Contraceptives

Behavioral Surgical
Non-Hormonal
Hormonal (Natural Family
Non-Oral ( Sterilization)
Planning)

Condoms
Oral Non-oral

Cervical Caps
Transdermal
COCs Patch
Diaphragm
POPs Vaginal Ring
Sponge
Depot injection

Progesterone Spermicides
containing IUD
Copper T IUD
Implants
 Factors in Selecting Contraception
1. Effectiveness
2. Importance of not being pregnant
3. Likelihood and ability to adhere
4. Patient-specific factors (e.g.smoking status, and concomitant diseases or
medications)
5. Age: Age may affect adherence or adverse effect risks
6. Cost and ability to pay
7. Adverse effects
8. Perceptions, misperceptions, risk-benefit
9. The reliability of the patient in using the method correctly (which may affect the
effectiveness of the method)
10. Noncontraceptive benefits
Oral Hormonal Contraceptives
• long-acting reversible contraception (LARC) methods vs. COC:
• LARC: implants, intrauterine methods and depot injections, offer
highly effective and cost-effective pregnancy prevention across the
reproductive lifespan
• COC remains the most commonly used method…?
Oral Hormonal Contraceptives
1. Combination Oral Contraceptives (COCs)
• COCs contain a synthetic estrogen and one of several steroids with
progestational activity

Most oral contraceptives contain one of three types of estrogen:

• ethinyl estradiol (EE), which is pharmacologically active
• mestranol, which is converted by the liver to EE
• estradiol valerate, which is metabolized to estradiol
Oral Hormonal Contraceptives
Combination Oral Contraceptives (COCs)
Progestins examples:
• Norethindrone
• Norethindrone acetate
• Ethynodiol diacetate
• Norgestrel
• Levonorgestrel
• Desogestrel
• Norgestimate
• Drospirenone
• Dienogest
Oral Hormonal Contraceptives
• With perfect-use OCs have a 99% efficacy rate, but with typical-use up
to 8% of users may become pregnant
Mechanism of action
• The primary mechanism by which COCs prevent pregnancy is through
inhibition of ovulation
• The estrogen component of COCs is most active in inhibiting FSH
release
• At sufficiently high doses, estrogens also may cause inhibition of LH
release.
• In low-dose COCs, the progestin component causes suppression of LH
Mechanism of action
• Ovulation is prevented by this suppression of the midcycle surge of
both FSH and LH and mimics the physiologic changes that occur
during pregnancy

• In addition to inhibiting ovulation, COCs induce changes in the

cervical mucus and endometrium that make sperm transport and
implantation of the embryo unlikely
Hormones in the combined pill
• The amount of EE used in COCs has decreased progressively and most now
contain 35 mcg or less of EE

• In an attempt to minimize the undesirable androgenic side effects associated with

the progestins of COCs, the original synthetic progestins were modified to create
“third generation” progestins (eg, desogestrel and norgestimate), and newer
progestins with antiandrogenic properties (eg, drospirenone) have been
discovered

• Overall, the synthetic progestins found in today’s COCs are extremely potent in
their ability to inhibit ovulation and prevent pregnancy
Hormones in the combined pill
• Third-generation progestins have no estrogenic effects and
are less androgenic than levonorgestrel, and thus are
thought to have fewer side effects (eg, less likelihood or
severity of acne)

• Drospirenone may also cause less weight gain compared

with levonorgestrel
 Contraindication of COCs
❑ Age ≥35 years and smoking ≥15 cigarettes per day.
❑ <21 days postpartum.
❑ Hypertension :SBP ≥160 mm Hg or DBP ≥90 mm Hg.
❑ Multiple CAD risk factors (ischemic heart disease, stroke, complicated valvular
disease).
❑ Current/prior venous thromboembolism (VTE).
❑ Long-standing/complicated diabetes.
❑ Migraine with aura.
❑ Breast cancer.
❑ severe cirrhosis, hepatocellular adenoma, or malignant hepatoma.
❑ Personal History of Cholestasis with Previous COCs use.
Patients should be instructed to immediately discontinue CHCs if they experience
warning signs, described as ACHES (abdominal pain, chest pain, headaches, eye
problems, and severe leg pain)
 Drug Interactions with OCs
• Anticonvulsants (carbamazepine, oxcarbazepine,
Medication phenytoin, phenobarbital, primidone, topiramate, and
felbamate)

• Increase metabolism of COCs via induction of various

Mechanism cytochrome P-450 enzymes

• Decrease efficacy of COCs (EE doses < 35 mcg

Clinical Effect are not recommended in women on these
medications)
 Drug Interactions with OCs
• Griseofulvin
• Modafinil
Medication
• Rifampin, rifabutin
• St. John’s wort

Mechanism • Increase metabolism of COCs

• Decrease efficacy of COCs; backup method of

contraception is recommended
Clinical Effect • avoid use of St. John’s wort with COCs
 Drug Interactions with OCs
• Benzodiazepines (alprazolam)
• Corticosteroids (hydrocortisone, methylprednisolone,
Medication prednisone)
• Theophylline
• Selegiline

• COCs may inhibit metabolism of alprazolam and

corticosteroids
Mechanism • Decrease selegiline metabolism
• COCs decrease theophylline clearance by 34% and increase
half-life by 33%

• Increase side effects of these drugs

Clinical Effect • May adjust dose if needed
 Drug Interactions with OCs
Medication • Lamotrigine

Mechanism • COCs increase metabolism of lamotrigine

Clinical Effect • Decrease efficacy of lamotrigine;

dose adjustment may be necessary
 Adverse Effects of Oral Contraceptives and Their Management
Adverse Effect Cause Adjustment
Spotting/bleeding Insufficient Monophasic with increased
before progestin progestin or triphasic with
finishing active pills increasing progestin

Continued bleeding Insufficient Increase estrogen or triphasic

after menses estrogen with lower early progestin

Midcycle bleeding Difficult to Increase estrogen and progestin

determine
Increased breakthrough Insufficient Increase estrogen or triphasic
bleeding estrogen formulation
in general
 Adverse Effects of Oral Contraceptives and Their Management
• Most clinicians will recommend that patients continue the same COC for at
least 3 months if breakthrough bleeding or spotting is the only complaint,
because this complication usually resolves within 3 months
• If intermenstrual bleeding continues late in her cycle after 3 months,
another COC with the same estrogen activity, more progestin activity, and
low androgen activity should be prescribed.
• Desogestrel 0.15 mg/EE 30 mcg (Desogen, Ortho-Cept, Apri, Reclipsen)
would be a good choice because progestational activity would be increased
and estrogenic activity would be maintained with minimal androgenic
liability
• If the woman experienced intermenstrual bleeding early in the cycle after
several months of use, she should be changed to a formulation with a
higher ratio of estrogen to progestin such as norethindrone
0.4mg/EE35mcg(Ovcon-35,FemconFe, Balziva, Zenchent).
 Adverse Effects of Oral Contraceptives and Their Management
Adverse Effect Cause Adjustment

Acne, PMDD, Progestin with higher Switch to progestin with

hirsutism androgenicity (eg, lower androgenicity such as
norgestrel, norgestimate, norethindrone or
levonorgestrel) drospirenone
Nausea, Related to estrogen Take at bedtime or with food;
vomiting decrease estrogen or switch to a
progestin-only product
GI symptoms often resolve in
1–3 months
Constipati- Related to progestin Decrease progestin
on,bloating, GI symptoms often resolve in
distention 1–3 months
 Adverse Effects of Oral Contraceptives and Their Management
Adverse Effect Cause Adjustment

Weight gain, Excess estrogen and Decrease estrogen and

fluid retention progestin switch to progestin with
with higher lower androgenicity such as
androgenicity (eg, norgestimate, norethindrone or
norgestrel, drospirenone
levonorgestrel)
Decrease vaginal Insufficient estrogen Increase estrogen or consider
lubrication vaginal hormonal ring
(NuvaRing)
Types of the combined pill
• COCs are available in monophasic, biphasic, triphasic, and quadriphasic
preparations

• Monophasic preparations contain fixed doses of estrogen and progestin in each

active pill

• Biphasic, triphasic, and quadriphasic preparations contain varying proportions of

one or both hormones during the pill cycle

• These preparations were introduced to reduce a patient’s cumulative exposure to

progestins, as well as to mimic more closely the hormonal changes of the
menstrual cycle. However, there is no evidence to suggest that the multiphasic
preparations offer any significant clinical advantage over monophasic pills
 COCs

Monophasic Biphasic Triphasic

Microcept® EE 30mcg + Levonorgestrel 0.15mg

Intermediate androgenic effect Cyclo- Triocept
21 tabs
Progynova®
Mercilon® EE 20mcg + Desogestrel 0.15mg
Low androgenic effect
21 tabs
Marvelon® EE 30mcg + Desogestrel 0.15mg
X
21 tabs Low androgenic effect Not a
Cilest® EE 35 mcg + Norgestimate 0.25mg
low androgenic effect
contaceptive
21 tabs
Gynera® EE 30 mcg + Gestodene 0.075mg
21 tabs
Yaz® EE 20mcg + Drospirenone 3mg
Antiandrogenic progestin
28 tabs
Yasmin® Norocarmena®EE 30mcg + Drospirenone 3mg
21 tabs 21 tabs Antiandrogenic progestin
The different available COCs cycle lengths
Extended or
21-DAY 24-DAY Continuous- Cycle
21-Day 21+7 (28- Day) • Contains 24 days of active • Adv: often prescribed in
pills followed by 4 days of women with underlying
•Contains 21 days of placebo. conditions including
• Contains only the • Adv: shorten menses and
active pills) followed ✓ Anemia, dysmenorrhea
active pills. by 7 days of placebo minimize the hormonal
withdrawal side effects (less cramps with fewer
• Take one pill daily pills.
(e.g., headaches, mood menstrual cycles),
for 21 days and then •Adv: minimize
take nothing for 1 changes) that some women ✓ menorrhagia (heavy
confusion; the patient experience during the menstrual bleeding)
week.
takes one pill daily placebo week.
• Adv: It is preferred regardless of whether ✓ endometriosis (to
when continuous decrease hormone
it is an active or
ovarian suppression fluctuations that affect
(Extended Cycle ) is placebo pill. After
taking the last pill of a endometrial tissues).
indicated to treat
estrogen-dependent 28-day pack, the
disorders such as patient should begin a
endometriosis new pack the next day.
When to start the COC?
Start the first cycle of COCs according to the manufacturer’s package instructions or
according to one of the following recommendations :

Sunday start: Take the first

Quick start: Take the first Day 1 start: Take the first tablet in the COC pack on the
first Sunday after the
COC tablet as soon as possible tablet in the COC pack on the
beginning of menstruation. If
regardless of cycle day. first day of menses
menses begins on Sunday,
start that day.
WHEN TO USE A BACKUP METHOD OF CONTRACEPTION

• Some clinicians recommend that a woman use an alternative method

of contraception for the entire first COC cycle.
• Others believe that alternative methods of contraception are
unnecessary if the COC is started on or before the fifth day of the
menstrual cycle.
• Most COC package inserts with the exception of Natazia (estradiol
valerate/dienogest) state that a backup method of contraception
(e.g., male or female condoms, spermicides, diaphragms) is not
necessary if patients use the day 1 start method
WHEN TO USE A BACKUP METHOD OF CONTRACEPTION

• If patients use the Sunday or quick start methods, backup

contraception should be used for the first week of the COC cycle
• A backup method is also recommended when doses are missed
COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• If a woman forgets to take one pill, she must take it as soon as she
remembers
• For the majority of COCs, most manufacturers recommend that if
she forgets to take one pill, she should take two pills on the day she
remembers
• Then she should take the remaining pills as usual
• A backup method of contraception is not necessary
COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• If she misses two pills in a row in week 1 or 2 of her pack, she must
take two pills on the day she remembers and two pills the next day
• She should use an alternative method of contraception for 7 days
after missing the pills and may consider emergency contraception
COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• If she misses two pills in a row in week 1 or 2 of her pack, she must
take two pills on the day she remembers and two pills the next day
• She should use an alternative method of contraception for 7 days
after missing the pills and may consider emergency contraception
COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• If a woman misses two pills in a row during the third week (for day
1 starters), she must discard the rest of the pack, start a new pack
on that same day, and use an alternative contraceptive method
for 7 days
COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• For Sunday starters, she should keep taking one pill every day until
Sunday, then start a new pack on Sunday.
• She must use an alternative method of contraception for 7 days after
missing the pills and may consider emergency contraception.
• She may miss her menstrual period this month.
 COC ADMINISTRATION AND MISSED
DOSE INSTRUCTIONS
• If a woman misses three or more pills in a row during the first 3 weeks (for day 1
starters), she must discard the rest of her pack, start a new pack that same day, and
use an alternative method of contraception for 7 days

• Sunday starters should keep taking one pill every day until Sunday, start a new pack
on Sunday, and use an alternative method of contraception for 7 days after missing
the pills, and they may consider emergency contraception.

• She may not have a menstrual period this month. If two pills are missed from a low-
dose COC (less than EE 30 mcg), some references suggest following the instructions
as if three pills were missed