Contraception
Dr. Khaled Alakhali PhD
Introduction
✓ Contraception is the prevention of pregnancy following sexual
intercourse by inhibiting sperm from reaching a mature ovum.
✓ Method failure is a failure inherent to the proper use of the
contraceptive alone.
✓ User failure takes into account the user’s ability to follow
directions correctly and consistently.
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The Menstrual Cycle
✓ The median length of the menstrual cycle is 28 days (range 21
to 40).
✓ The first day of menses is day 1 of the follicular phase.
✓ Ovulation usually occurs on day 14 of the menstrual cycle.
✓ After ovulation, the luteal phase lasts until the beginning of the
next cycle.
✓ Epinephrine and norepinephrine stimulate the hypothalamus to
stimulates the anterior pituitary to secrete bursts of
gonadotropins, follicle-stimulating hormone (FSH), and
luteinizing hormone (LH).
✓ In the follicular phase, FSH causes follicles for continued
growth. Between 5 and 7 days, one of these becomes the
dominant follicle, which later ruptures to release the oocyte.
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The Menstrual Cycle
✓ The dominant follicle develops increasing amounts of estradiol
and inhibin, which cause a negative feedback on the secretion
of FSH.
✓ The dominant follicle continues to grow and synthesizes
estradiol, progesterone, and androgen.
✓ FSH regulates aromatase enzymes that induce conversion of
androgens to estrogens in the follicle.
✓ The pituitary releases a mid-cycle LH surge that stimulates the
final stages of follicular maturation and ovulation.
✓ Ovulation occurs 24 to 36 hours after the estradiol peak and
10 to 16 hours after the LH peak.
✓ The LH surge, occurring 28 to 32 hours before a follicle
ruptures, is the most clinically of ovulation.
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The Menstrual Cycle
✓ Conception is most successful when intercourse takes place
from 2 days before ovulation to the day of ovulation.
✓ After ovulation, the remaining luteinized follicles become the
corpus luteum, which synthesizes androgen, estrogen, and
progesterone.
✓ If pregnancy occurs, human chorionic gonadotropin prevents
regression of the corpus luteum and stimulates continued
production of estrogen and progesterone.
✓ If pregnancy does not occur, the corpus luteum degenerates,
and progesterone declines. Then menstruation occurs.
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Treatment
Non-pharmacologic Therapy
A comparison of methods of nonhormonal contraception
✓ Condoms, male
✓ Condoms, female (Reality)
✓ Cervical cap (Fem Cap, Leah’s Shield)
✓ Spermicides alone
✓ Sponge (Today)
Periodic Abstinence
✓ The abstinence (rhythm) method is not well accepted, as
it is associated with relatively high pregnancy rates and
avoidance of intercourse for several days in each cycle.
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Treatment
Non-pharmacologic Therapy
Barrier Techniques
✓ The effectiveness of the diaphragm depends on a barrier and
on the spermicidal cream or jelly placed in the diaphragm
before insertion.
✓ The cervical cap, can be inserted 6 hours prior to intercourse,
and women should not wear the cap for longer than 48 hours
to reduce the risk of toxic shock syndrome.
✓ Most condoms made of latex rubber, which is not
impermeable to viruses.
✓ Mineral oil–based vaginal drug formulations can decrease
barrier strength of latex by 90% in 60 seconds.
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Treatment
Non-pharmacologic Therapy
Barrier Techniques
✓ Condoms with spermicides are no longer recommended,
due to no protection against pregnancy or STDs and may
increase to HIV.
✓ The female condom (Reality) covers the labia as well as
the cervix, thus it may be more effective than the male
condom.
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Pharmacologic Therapy
Spermicides
✓ Spermicides, are surfactants that destroy sperm cell walls.
✓ No protection against STDs, and when used more than two
times daily, also increase the transmission of HIV.
✓ Women at high risk for HIV should not use spermicides.
Spermicide-Implanted Barrier Techniques
✓ The vaginal contraceptive sponge (Today) provides protection
for 24 hours.
✓ After intercourse, the sponge must be left in place for at least
6 hours before removal.
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Hormonal Contraception
Composition and Formulations
✓ Hormonal contraceptives contain either a combination of
estrogen and progestin or a progestin alone.
✓ Progestins thicken cervical mucus, delay sperm transport, and
induce endometrial atrophy.
✓ Progestins also block the LH surge and thus inhibit ovulation.
✓ Estrogens suppress FSH release, which may contribute to
blocking the LH surge.
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Hormonal Contraception
Components
✓ Two synthetic estrogens are used in hormonal contraceptives,
ethinyl estradiol (EE) and mestranol.
✓ Mestranol must be converted to EE in the liver to be active. It is
approximately 50% less potent than EE.
✓ Most combined oral contraceptives (OCs) contain estrogen at
doses of 20 to 50 mcg of EE daily.
✓ Progestins vary in activity and differ with respect to inherent
estrogenic, antiestrogenic, and androgenic effects.
✓ Their estrogenic and antiestrogenic properties occur due to
progestins are metabolized to estrogenic substances.
✓ Androgenic properties occur because of the structural similarity of
the progestin to testosterone.
Please refer to any text book for lists available OCs by brand name and hormonal composition.
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Pharmacologic Therapy
Considerations with Oral Contraceptive Use
✓ Recommendation of the American College of Obstetricians
and Gynecologists is to allow after a medical history and blood
pressure measurement.
✓ Non-contraceptive benefits of OCs include:
✓ Decreased menstrual cramps and ovulation pain
✓ Decreased menstrual blood loss
✓ Improved menstrual regularity
✓ Increased hemoglobin concentration, Improvement in acne
✓ Reduced risk of ovarian and endometrial cancer
✓ Reduced risk of ovarian cysts
✓ Reduced ectopic pregnancy
✓ Reduced pelvic inflammatory disease, and
✓ Reduced benign breast disease.
✓ The transdermal patch may cause less breast discomfort and
dysmenorrhea than OCs.
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Adverse effects associated with combined
hormonal contraceptives (CHCs)
Estrogen excess
✓ Nausea, breast tenderness, headaches, weight gain,
dysmenorrhea, menorrhagia, and uterine fibroid growth
Estrogen deficiency
✓ Vasomotor symptoms, nervousness, decreased libido.
Progestin excess
✓ Increased appetite, weight gain, bloating, constipation.
✓ Acne, oily skin, hirsutism. depression, fatigue, irritability
Progestin deficiency
✓ Dysmenorrhea, menorrhagia.
The main safety concern about CHCs is their lack of protection
against STDs.
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Women over 35 Years of Age
✓ CHCs containing less than 50 mcg EE are an acceptable
form of contraception for nonsmoking women up to the
time of menopause.
✓ Increased risk of myocardial infarction or stroke in
healthy, nonsmoking women older than 35 years of age
using low-dose OCs.
Smoking Women:
✓ Women over 35 years who smoke and take OCs have an
increased risk of MI and stroke.
Hypertension:
✓ In women with hypertension, OCs have been associated
with an increased risk of MI and stroke.
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Women over 35 Years of Age
Diabetes:
✓ Nonsmoking women younger than 35 years with diabetes, but
no vascular disease, can safely use CHCs, but diabetic women
with vascular disease should not use OCs.
Dyslipidemia:
✓ Progestins decrease high-density lipoprotein (HDL) and
increase low-density lipoprotein (LDL).
✓ Estrogens decrease LDL but increase HDL and triglycerides.
Thromboembolism:
✓ Estrogens have development of venous thromboembolism and
pulmonary embolism.
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Women over 35 Years of Age
Migraine Headache:
✓ Women with migraines may experience a decreased or
increased frequency of migraine headaches when using CHCs.
Breast Cancer:
✓ The WHO precautions state that women with recent personal
history of breast cancer should not use CHCs, but that CHCs
can be considered in women without evidence of disease for 5
years.
Systemic Lupus Erythematosus (SLE):
✓ CHCs should be avoided in women with SLE and
antiphospholipid antibodies. Progestin-only contraceptives can
be used in these women.
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Choice of an Oral Contraceptive
✓ Adolescents, underweight women 50 kg, women older than 35
years, and those who are perimenopausal may have fewer side
effects with OCs containing 20 to 25 mcg of EE.
✓ Women weighing more than 72.7 kg may have higher
contraceptive failure rates with low-dose OCs and may benefit
from pills containing 35 to 50 mcg of EE.
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Choice of an Oral Contraceptive
Women with:
✓ Migraine headaches
✓ History of thromboembolic disease
✓ Heart disease
✓ Cerebrovascular disease
✓ SLE with vascular disease, and
✓ Hypertriglyceridemia
✓ They are good candidates for progestin-only methods.
✓ Women older than 35 years who are smokers or are
obese, or hypertension or vascular disease, should use
progesterone-only methods.
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Managing Side Effects:
✓ Many symptoms occurring in the first cycle of OC use:
✓ Bleeding
✓ Nausea
✓ Bloating
✓ Improve by the second or third cycle of use.
✓ Women should be instructed to immediately discontinue
CHCs if they experience warning signs often called
ACHES (abdominal pain, chest pain, headaches, eye
problems, and severe leg pain).
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Drug Interactions:
✓ Rifampin reduces the efficacy of OCs.
✓ Case reports have shown a reduction in EE levels when CHCs
are taken with tetracyclines and penicillin derivatives.
✓ Phenobarbital, carbamazepine, and phenytoin reduce efficacy of
OCs, and many anticonvulsants are known teratogens.
✓ The use of condoms in conjunction with high-estrogen OCs
or intrauterine devices (IUDs) may be considered for women
taking these drugs.
Please refer to any text book for drug interaction for lists available OCs and CHCs.
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Discontinuation of the Oral Contraceptive,
Return of Fertility
✓ Traditionally, women are advised to allow two to three normal
menstrual periods after discontinuing CHCs before becoming
pregnant.
✓ The average delay in ovulation after discontinuing OCs is 1 to
2 weeks
Emergency Contraception
✓ Plan B is the only product FDA approved for EC and is the
regimen of choice. Plan B contains two tablets, each containing
0.75 mg levonorgestrel. The first tablet is to be taken within 72
hours of unprotected intercourse (the sooner, the more
effective); the second dose is taken 12 hours later.
✓ Common side effects of EC are nausea, vomiting, and irregular
bleeding.
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Transdermal Contraceptives
✓ A combination contraceptive is available as a transdermal
patch, which may have improved adherence compared to OCs.
✓
✓ The patch should be applied to the abdomen, buttocks, upper
torso, or upper arm at the beginning of the menstrual cycle
and replaced every week for 3 weeks.
✓ Preliminary data indicating a higher incidence of
thromboembolic events with the patch.
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Contraceptive Rings
✓ The first vaginal ring releases 15 mcg/day of EE and 120
mcg/day of etonogestrel over a 3-week period.
✓ On first use, the ring should be inserted on or prior to the
fifth day of the cycle, remain in place for 3 weeks, then be
removed.
✓ One week should lapse before the new ring is inserted on the
same day of the week as it was for the last cycle.
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Long-Acting Injectable and Implantable
Contraceptives
✓ Women who benefit from progestin-only methods, are those who
are breast-feeding, those who are intolerant to estrogens, and those
with concomitant medical conditions in which estrogen is not
recommended.
✓ Also injectable and implantable contraceptives are beneficial for
women with compliance issues.
Injectable Progestins
✓ DMPA (depot-medroxyprogesterone acetate) 150 mg administered
by deep IM within 5 days of the onset of menstrual bleeding inhibits
ovulation for more than 3 months.
✓ The dose should be repeated every12 weeks to ensure continuous
contraception.
✓ A new formulation contains 104 mg of DMPA, which is injected
subcutaneously into the thigh or abdomen.
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✓ DMPA can be given immediately postpartum in women
who are not breast-feeding, but in women who are
breast-feeding, it should not be given until 6 weeks
postpartum.
✓ Adverse effect of DMPA is:
✓ Menstrual irregularities
✓ Breast tenderness
✓ Weight gain
✓ Depression
✓ Osteoporosis
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Subdermal Progestin Implants
✓ Implanon is a single, 4-cm implant (plastic rod), containing 68 mg of
etonogestrel that is placed under the skin of the upper arm.
✓ It releases 60 mcg daily for the first month, decreasing gradually to
30 mcg/daily at the end of the 3 years of recommended use.
✓ With perfect efficacy 100%, but may be less in women weighing
more than 130% of their ideal body weight.
✓ Adverse effect is irregular menstrual bleeding. Other side effects are
headache, vaginitis, weight gain, acne, and breast and abdominal pain.
✓ It is contraindicated in women who are pregnant, have active liver
disease, a history of thromboembolic events, or a history of breast
cancer.
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Intrauterine Devices
✓ IUDs cause low inflammation and increased prostaglandin
formation.
✓ Endometrial suppression is caused by the progestin-releasing
IUD.
✓ Efficacy rates are greater than 99%.
✓ Pelvic inflammatory disease is highest during the first 20 days
after the insertion procedure.
✓ ParaGard (copper) can be left in place for 10 years. A
disadvantage is increased menstrual blood flow and
dysmenorrhea.
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Evaluation of Therapeutic Outcomes
✓ Glucose levels should be monitored closely when CHCs are
started in patients with a history of diabetes mellitus.
✓ Contraceptive users should have at least annual screening, and
they should also be regularly evaluated bleeding, amenorrhea,
weight gain, and acne.
✓ Women using DMPA should be evaluated every 3 months for
weight gain, menstrual cycle disturbances, and STD risks.
✓ Patients on DMPA also should be weighed, have their blood
pressure monitored, and have a physical exam, and
Papanicolaou smear annually, as well as mammogram as
indicated based on the patient’s age.
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Reference
✓ Pharmacotherapy-By Joseph T.Diprio,9th edition.
✓ Pharmacotherapy A Pathophysiologic Approach-by
Joseph-T.Diprio 9th Edition.
✓ Pharmacotherapy Principles & Practice 4th edition
Marie A. Chisholm, Joseph-T. Diprio
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