Contraceptionby

Magdy M.Awny, PhD

An overview

Today, the voluntary control of fertility is of paramount importance to modern

society. From a global point of view, countries currently face the crisis of rapid

population growth that has begun to threaten human survival.

At the present the population of the world will double in 40 years; in several of the

more socioeconomically disadvantaged countries, populations will double in less

than 20 years.

On a smaller scale, effective control reproduction can be essential to woman’s

ability to achieve her individual goals and to contribute to her sense of well-being

Indications for Contraception:

I. Medical:

-Medical diseases of

the mother making

pregnancy hazardous

(e.g., heart diseases).

-Repeated Cesarean

sections.

II. Family

planning:

-Spacing of pregnancy.

-Choosing the

appropriate time to get

pregnant.

III. Social:

-Rape.

-Illegal relations.

Methods of Contraception

(birth control methods)

1) Combined estrogen and progestin pills (COCs), skin patch,

and vaginal ring.

2) Progestin-only pills (POP), injections, IUDs and implants.

* Long-acting reversible contraception (LARC):

the intrauterine device (IUD) and implant.

3) Emergency/Postcoital “morning after” contraceptives: pills and the copper IUD.

4) Barrier methods: the diaphragm, cervical cap, and condom (M & Fm).

5) Fertility awareness and periodic abstinence methods

e.g., periods of avoiding sex, coitus interruptus & Lactational Amenorrhea Method (LAM)

6) Surgery: Male & female sterilization. (vasectomy & tubal ligation)

Horm

onal c

ontra

ceptio

n

Oestrogen

&

Progestin.

Oral BC Pills

(COCs)

Transdermal

BC Patch

Vaginal BC

Ring

1-Combined Hormonal Contraceptives (oral pills, skin patch, vaginal ring)

The estrogenic component is usually ethinyl estradiol but a few preparations contain

mestranol (e.g., norinyl-1)

Examples of progestins include:

1st generation……. ethynodiol, norethindrone acetate &medroxyprogesterone acetate (MPA)

2nd generation……. norethisterone, levonorgestrel

3rd generation……. Desogestrel, etonogestrel, norelgestromin, gestodene, and norgestimate

4th generation……..drospirenone (Yasmin® & Yaz®) (has progestogenic, antiandrogenic and

antimineralocorticoid activity i.e k+ sparing effect).

NB:- 3rd &4th generations have less androgenic activity (so suitable in women with acne, hirsutism, breast

tenderness, breakthrough bleeding & weight gain) but with high risk for venous thromboembolism than 1st & 2nd

How do combined hormonal BC methods prevent pregnancy? (Mechanism of action)

These methods release oestrogen and progestin leading to:

1-Stopping ovulation

by suppressing the release of gonadotropins (FSH & LH) so inhibit follicular development and prevent ovulation

2-progestin→↑ the viscosity of cervical mucus making it hard for sperms to

enter the uterus. i.e. decrease sperm viability and penetration

3-Thinning of uterine lining, making it less likely that a fertilized ovum can

implant into it i.e. endometrial atrophy.

4-Disturbing the coordinated contractions of the cervix, uterus and tubes that

help transport of sperm to ovum i.e. slowing tubal motility

Efficacy of combined hormonal BC methods?

1- With perfect use (the method is used correctly each time),

the failure rate (i.e. chance of pregnancy) will be < 1% during the 1st year of use

( > 99% efficacy).

2-With typical use (i.e. method may not always be used correctly each time),

the failure rate reaches 9% during the 1st year

(91% efficacy).

Can combined hormonal BC methods be used during breast feeding?

Because estrogen may affect milk supply, it is recommended to use combined hormonal

methods 5 weeks after delivery when breastfeeding has been well established.

Benefits (uses) of combined hormonal BC methods (contraceptives)?

1. Make the period more regular, lighter, and shorter.

2. Help in reduction of menstrual cramps (dysmenorrhea), mittleschmerz.

3. Decrease the risk of cancer of uterus, ovary and colon. (COCs cause 50%↓ in endometrial adenocarcinoma

risk for at least 15 years following stopping of use)…breast cancer risk?

4. Treatment of fibroid & endometriosis-associated heavy bleeding & menstrual pain.

5. They may improve acne and reduce hirsutism……Diane 35

6. To prevent heavy bleeding (menorrhagia) and pain by stopping the menstrual period.

7. can reduce the frequency of period-associated migraine attacks ??

8. Used to avoid mense during certain events e.g. Huj/Umra & vacations by skipping placebo pill week

9. Prevention of pregnancy.

Adverse effects and possible risks of combined hormonal BC methods?

1-cardiovascular effects:

e.g. cerebral, coronary thrombosis & hypertension, so COCs cause small increased risk of

DVT, heart attack and stroke

2- Change in serum lipids

Estrogen→ ↑HDL, ↓LDL cholesterol [good effect]

Progestins →↑ LDL /HDL ratio, TG

So estrogen dominant preparation is best used for pt with elevated serum cholesterol?

3-metabolic effects • ↓ intestinal absorption of carbohydrate

• ↓ glucose tolerance & ↑fasting blood glucose

• Wt gain

Other adverse effects:

• Breast fullness, suppression of lactation, depression, nausea, vomiting & ↓libido

• Fluid retention (hypertension) due to estrogen induced ↑ rennin activity & hence aldosterone secretion

• Amenorrhea, Hyperpigmentation of face [chloasma], hairsutism, acne [due to androgenic activity of progestins]

& breakthrough bleeding

• headache, vaginal infection

• Increase level of plasminogen, fibrinogen, and clotting factors VII, VIII, IX & X

C.I.

A-Combined oral contraceptive pills

Classified into:

1-monophasic combination pills:

Contain fixed dose of estrogens and progestogen in each active pill

Dosing start from 1st day of cycle for 21 days followed by 7 days of pill free period.

Some preparations are available as 28 days pills with 7 day placebo pills containing

only iron or inert substance

Types:

-Low estrogen /low progestin pills:(Nordette®, microcept) E. estradiol 0.03 mg /levonorgestrel 0.15mg .lowest side effect of estrogen

-Low estrogen/high progestin pills: (lostrin®) E. estradiol 0.03 mg / norethisterone 1.5mg

(Yasmin ®) E. estradiol 0.030 mg / drospirenone 3 mg

-High estrogen /high progestin pills:(ovral®) E. estradiol 0.05 mg / levonorgestrel 0.5 mg

Nausea,

Wt gain,Breast

tenderness

E. estradiol o.03mg + Gestodene 0.075mgE. estradiol o.035mg + norgestimate 0.25 mg

-Example of triphasic preparation is triocept® : 21 days active pills staring on 1st day bleeding (first use)

+ 7days free pills then resume next course

1st phase (6 days): pills have 30 ug eth. estradiol + 50 ug levonorgestrel start 1st packet on day 1 of menses

2nd phase (5 days ): pills have 40ug eth. estradiol + 75 ug levonorgestrel

3rd phase(10 days) :pills have 30ug eth. estradiol + 125 ug levonorgestrel

2-biphasic&triphasic combination pills (sequential pills):

-They provide 2 or 3 different pills respectively containing different doses of estrogen and progestins, to be taken

at different time intervals during the cycle to simulate the natural hormones ration during the cycle

-Are effective but with side effect e.g. spotting ,breakthrough bleeding

E. Estradiol 0.035mg

Norethindrone 0.5mg/1o, 1mg/11

Different types of combined hormonal pills and how they are taken

COCs

21-day pills

28-day pills

91-day pills

365-day pills

one pill at the same time each day for 21days.

Wait 7 pill free days before starting a new pack (mense

occurs).

one pill at the same time each day for 28days. Depending on

the brand, the 1st 21 pills or the 1st 24 pills contain estrogen and

progestin. The remaining pills may be (a) Estrogen-only pills, (2) Iron-

containing pills without hormones (during it mense starts)

one pill at the same time each day for 84 days.

the remaining 7 pills either contain no hormones or contain estrogen only. The period will occur in the

days of combined hormone-free pills every 3 months (i.e. 4 times/year).

one pill at the same time each day for a year.

The period become lighter and may even stop.

Seasonale®,

seasonique®

Lybrel®

Gynera®

YAZ®

Starting methods of BCPs?For the initial cycle of therapy:

1-First day start

First active pill is taken during the first day of period and continued

at the same time of day. No back-up method is required

2-Fifth day start:

Wait until the fifth day of your period to take your first active pill. Use backup method 7d

3-Sunday start links up with most contraception calendars, convenient so that you do not forget to take the pill

First pill is taken on Sunday after the period starts (if cycle starts Sunday take first pill at that

same day) if Sunday is not the first days of period …..wait until ! First Sunday after menses started

To take first pill and use a back-up method for 7 days (till next Sunday)

4-Today start

Start the pill today. If you have had unprotected sexual intercourse since your last period,

perform a pregnancy test prior to starting the pill. If it is negative, start the pill today.

Use back-up method for ! first 7 days of the first use.

What can the woman do if she forget to take a pill?

1-If a woman misses 1 active pill (not > 24hr elapsed)take tablet as soon as it is remembered, take the next tab at ! regular time

i.e. 2 tabs may be taken in one day

2-If two active pills are missed

take two tablets a day for next 2 days to cover the missed pills, then resume

regular dosing schedule.

3-If > 2 active pills i.e. 3 consecutive days are missed (cilest ® at wk1,2or3)

-discontinue drug and substitute other contraceptive method until period

begins. Then start new packet of tablets.

-throw out the rest of pack and start anew one that same day & use back-up

method until 7 active pills taken without interruption

** any missed placebo tab (week 4) should be thrown away , keep taking one pill

until pack is empty

Triphasic

1,2 Like

above

but use

backup

method

till next

cycle

Drug interaction with oral contraceptives

-They ↓ hypoprothrombinaemic effect of coumarins? as they ↑blood Clotting Factors level

-They ↓efficacy of hypocholestrolaemic drugs?→ as they ↑cholesterol, TG

-They ↓effect of antihypertensive drugs ? →as they ↑rennin activity & aldosterone secretion

-Their effect is ↓[so pregnancy may occur] in women taking

A-liver enzyme inducer e.g. phenytoin, rifampicin, carbamazepine

B-paraffin oil that ↓intestinal absorption of OCs

B- The combined BC vaginal ring

It is a flexible, plastic ring that is placed in the upper vagina.

It releases estrogen (ethinyl estradiol) and progestin (etonogestrel) that are absorbed through

the vaginal tissues into the body.

NuvaRing®

How can the vaginal ring be used?

-The ring is folded and inserted into the upper vagina by the woman.

-It stays there for 21 days then removed. The woman waits for 7 days (during which the period occurs)

before inserting a new ring.

-For continuous contraception use, a ring is inserted every 21 days without ring-free week in between.

What are possible side effects of the vaginal ring? Headache Nausea Breast tenderness

Vaginal discharge, Vaginal irritation

Breakthrough bleeding.

A disadvantage of the vaginal ring is that it may occasionally slide or be expelled accidentally

C- The contraceptive skin patch (Evra®)

it releases estrogen (ethinyl estradiol, 0.75 mg) and

progestin (norelgestromin 6 mg “3rd G” ) transdermally into the body.

The patch is less effective in women weighing > 90 kg

How to use?

The patch is applied to the buttocks, upper back, upper arm, abdomen or chest

(except the breasts).

•One patch is applied weekly for 3 successive weeks (21 days), week 4 is patch free

where the period takes place. After week 4 a new patch is applied and the cycle is repeated.

•The patch is applied on the same day of the week even if the woman is still menstruating.

•For continuous contraception, apply a new patch every week on the same day without interruption.

side effects: as above + Skin irritation

1.75

sq inch

2-progestin-only birth control methods?

In contrast to combined BC methods, progestin-only BC

methods contains “progestin” as the only hormone. These methods include:

A. Oral pills (mini-pills)

B. Long-acting intramuscular injection

C. Subcutaneous implant LARC

D. Hormonal intrauterine device (IUD)

Progestin-only pills & injection have about the same effectiveness as combined BC methods.

With typical use failure rate is 7% in the first year of use

Mechanism of action:

like COCs but Stopping ovulation (not uniformly in all cycles) is not a consistent action

because about 40% of women using the mini-pills will continue to ovulate.

A- Progestin-only pills (Mini-Pills)Benefits:

1. They do not interfere with sex.

2. They may reduce or stop menstrual bleeding.

3. They are not associated with an increased risk of high blood pressure or CVD and

can be taken in conditions where combined methods can not be used such as

a history of DVT and uncontrolled hypertension.

**They can be used during breastfeeding, immediately after childbirth.

**they should not be used in women who have breast cancer or who have a history of breast cancer.

Side effects:

- Headache, Nausea, Breast tenderness,

- Unpredictable bleeding patterns (spotting, light, heavy or not at all)??. Lack of estrogen

Depo Provera

increase the

risk of CVD

How can progestin-only pills be taken?

• 28-day pills: All contain progestin.

• One pill is taken every day in the same time for 28 days, then start another pack without interruption.

• For maximal efficacy, the pill should be taken in the same time each day.

• The pills should be used even if the woman bleeds between periods or feels sick.

What can the woman do if she forget to take a pill?

1. If a pill is missed by >3 hours, the pill should be taken once remembered

in addition of using a backup method of contraception (e.g. condom) for the next 7 days

(Progestin takes 7 successive days to suppress ovulation).

2. If vomiting or severe diarrhoea occurs within 3 hours after taking a pill, the progestin

may not be absorbed completely, therefore a backup method is used until

2 days after stopping of vomiting or diarrhea.

Levonorgestrel 0.03 mg

Desogestrel 0.075mg),

B-Progestin-only injection (Depo-Provera®):

It is a depot (long-acting) IM injection containing 150 mg/ml of medroxyprogesterone acetate

it provides irreversible protection against pregnancy for 3-6 months.

Mechanism: like mini-pills

How the injection is used?

- the first injection can be given at any time during the cycle.

-Injection is given IM in buttocks every 12 weeks.

-The repeated injection can be given up to 2 weeks late.

If it is given > 2 weeks late, sexual intercourse should be avoided or a backup method is used for 7 days.

Possible side effects of the injection?

1-Irregular bleeding. 2-Weight gain (< 5 pounds).

3-Delayed fertility: it takes an average of 10 months for pregnancy to occur after stopping the injection

(18 months have been reported in some cases).

What are the benefits of the injection?

Long acting

Does not interfere with sex.

Reduced risk of uterine cancer with long-term use.

Reduction of endometriosis-associated pelvic pain.

Reduction of fibroid-associated vaginal bleeding.

Possible absence of period (secondary amenorrhoea).

No one can tell that the woman is using birth control.

What are possible risks of the injection?

• Osteoporosis (bone loss) with long-term-use (reversible)

• Women with a history of CVD are at increased risk of CVD while using the injection.

This increased risk may last for some time after the method is stopped.

A-progestin only pills (mini-pill

B-progestin only injection

C- Long-Acting Reversible Contraception (LARC) methods

1-Subcutaneous implant

2-Hormonal intrauterine device (IUD)

. Advantages:

Highly effective,

Long-acting (last for 3-5 years),

Can be removed at any time when pregnancy is desired.

Efficacy:

During the 1st year of typical use, < 1% of women using an IUD or an implant will become

pregnant, a rate similar to sterilization.

Over long-term use, LARC methods are 20 times more effective than the birth control pills,

patch and ring.

1-The progestin-only birth control implant:

• It is a single flexible rod about the size of a matchstick that is inserted under the

skin in the inner upper arm.

• It releases progestin and protects against pregnancy for up to 3 years.

• The implant should be replaced after 3 years and after 2 years if the woman’s BMI

is > 35 kg/m2.

e.g. Implanon®: is a single (40 mm x 2 mm) rod containing 68 mg of

etonogestrel released slowly over a 3 year period. It is inserted

subcutaneously into the inner upper arm under local anaesthesia.

Mechanism

• Stopping ovulation.

• Increasing the viscosity of cervical mucus so decrease sperm penetration

• Endometrial atrophy

Benefits of the birth control implant

1. It does not interfere with sex or daily activities.

2. Almost all woman can use the implant.

3. It can be inserted immediately after an abortion, a miscarriage, childbirth and during breastfeeding.

4. It can be simply removed when pregnancy is desired.

5. It may reduce menstrual pain.

6. It may cause amenorrhea in some women

7. It provides some protection against pelvic inflammatory disease (PID) and endometrial cancer.

Side effects of the BC implant

1. Irregular spotting which usually disappear within the 1st year (in 26%of women ).

2. Secondary amenorrhoea (in 20%of women within the 1st year).

3. Mood changes and depression.

4. Headache & Acne.

5. Weight gain in some women.

** The implant should not be used with enzyme inducers.

possible risks of the BC implant:

Rarely, pregnancy may occur in the presence of the implant (there is a slightly

increased risk to be an ectopic pregnancy).

D-The intrauterine device (IUD)(e.g. progestasert® & Mirena®)

It is a small flexible T-shaped plastic device that is inserted into and left inside the uterus.

Types of IUDs:

1) The hormonal IUD releases progestin. It is approved for use for 3-5 years

according to the brand and progestin type.

2) The copper IUD does not contain hormones. It is approved for use for up to 10 years.

The vertical arm of

the IUD contains a progestin

How does the IUD work?

IUDs work mainly by preventing fertilization of the egg by the sperm.

The hormonal IUD also thickens the cervical mucus making it hard for sperms to enter the uterus and

fertilizes the ovum, and keeps the uterine lining thin, making it less likely that a fertilized ovum can

implant into it.

The copper IUD inhibits fertilization through the toxic effects of copper on the sperm and developing

endometrium. It blocks both fertilization and implantation.

Benefits of the IUD (advantages):

1. It does not interfere with sex or daily activity & provide contraception for years .

2. No one can tell that the woman is using birth control.

3. Almost all women can use an IUD.

4. Reversible: can be easily removed when needed.

5. Reduction of menstrual pain and heavy bleeding (menorrhagia) (hormonal IUD).

6. The copper IUD is the most effective form of emergency contraception.

7. Reduced incidence of dysmenorrhea.

8. Less ADRs due to local action.

9. Not affected by enzyme-inducing drugs.

10. May be used by postmenopausal women on estrogen therapy to protect against endometrial

cancer.

Possible side effects of the IUD:

The copper IUD may cause menstrual pain and bleeding that usually decrease

within 1 year of use.

Hormonal IUDs may cause spotting, irregular bleeding and some menstrual pain in the 1st 3-6 months of

use. The menstrual bleeding, the length of the period and menstrual pain usually decrease overtime.

Hormonal IUDs may cause headache, nausea, depression and breast tenderness

Possible risks of the IUD (complications):

-Risk of expulsion (5% of users in the 1st year of use).

-Risk of uterine wall perforation during insertion (risk 1: 1000).

-Pelvic inflammatory disease (PID): an infection of the uterus and fallopian tubes

leading to scarring in the reproductive organs making pregnancy difficult (< 1%).

The risk of PID is slightly increased in the 1st 20 days after insertion.

-Rarely, pregnancy may occur in the presence of an IUD (there is a higher chance to

be an ectopic pregnancy).

-Increased risk of functional ovarian cysts.

Emergency Contraception (Postcoital or “Morning After” Contraception)

It is a birth control measures that if taken after unprotected sexual intercourse,

may prevent pregnancy.

It is indicated:

• When no contraception has been used.

• When the compliance with the usual method is poor (e.g., missed pill).

• When the usual method has failed (e.g., condom rupture).

• When a woman is raped.

Types:

1. Emergency contraception pills.

2. The copper IUD….inserted within 5 days of unprotected intercourse

If inserted within 72 hours…..gives 99% efficacy

Types of emergency contraception pills

1-The estrogen-only regimen:

-The estrogen-only regimen depends on the use of an oral oestrogen

(e.g., ethinyl estradiol or mestranol) within 72 hours of unprotected

intercourse twice daily for 5 days.

-It is inferior to other regimens of emergency contraception.

2-progestin-only emergency contraception pills (Plan B®)

It uses the progestin Levonorgestrel as soon as possible within 72 hrs of unprotected

intercourse in a dose of 1.5 mg either as a single dose or as two 750 μg doses 12-24 hours apart.

This regimen can be used more than once within the same menstrual cycle.

Efficacy:

95% efficacy if used within 24 hours and 85% if used later on within 72 hours.

It is of no value if pregnancy has started and have no effect on pre-existing pregnancy.

It prevents the pregnancy by inhibiting ovulation

Levonorgest 0.75 mg

3-Combination emergency contraception pills

Yuzpe regimen: Ethinyl estradiol, 100 μg, + Levonorgestrel, 500 μg,

-Taken within 72 hours of unprotected intercourse and repeated 12 hours later.

-it is inferior to POP (efficacy:75% versus 85%) and

-Associated with a higher incidence of nausea and vomiting.

-They are thought to work by preventing ovulation.

4- The Ulipristal emergency contraception regimen

-Ulipristal acetate (ella® or ellaOne®) 30 mg tablet:

is a selective progestin receptor modulator (SPRM) with a mixed agonist/antagonist activity.

- Has a constant efficacy if used within 120 hours (5 days) after intercourse

- Prevents pregnancy by delaying /blocking ovulation, inhibiting follicle rupture or delaying

the maturation of the endometrium.

-It is more effective than POP when taken as directed.

-Ulipristal should be taken only once during a cycle.

-It may decrease the efficacy of hormonal BC methods, therefore, a non-hormonal

method, such as a condom, should be used after taking Ulipristal until the next

menstrual cycle starts.

5-The mifepristone emergency contraception regimen:

-Mifepristone is a full progestin receptor antagonist.

-Mifepristone regimen: a single postcoital dose of 10 mg mifepristone (Mifeprex ®)

prevents pregnancy in 85% of cases if used within 5 days of unprotected intercourse.

-It is FDA-approved as an abortifacient (200-600mg).

-Mifepristone inhibits ovulation and blocks implantation by causing a delay

in the maturation of the endometrium.