CONTRACEPTION

[Link] Hamza AlShammari

[Link], F.I.C.M.S
Updated 2023
Introduction

• Contraception is the prevention of pregnancy by inhibiting sperm from reaching a

mature ovum or by preventing a fertilized ovum from implanting in the endometrium.

• While cis-women are the primary use of hormonal contraception, these agents are
also used by transgender individuals and this chapter has been written to reflect this.
MENSTRUAL CYCLE PATHOPHYSIOLOGY

• The median menstrual cycle length is 28 days (range 21–40 days). Day 1 is the first
day of menses and marks the beginning of the follicular phase. Ovulation usually
occurs on day 14, followed by the luteal phase that lasts until the beginning of the next
cycle.

• The hypothalamus secretes gonadotropin releasing hormone, which stimulates the

anterior pituitary to secrete the gonadotropins follicle-stimulating hormone (FSH) and
luteinizing hormone (LH).

• In the follicular phase, FSH levels increase and cause recruitment of a small group of
follicles for continued growth. Between days 5 and 7, one of these becomes the
dominant follicle, which later ruptures to release the oocyte.

• The dominant follicle develops increasing amounts of estradiol and inhibin, providing
a negative feedback on the secretion of gonadotropin releasing hormone and FSH.
• The dominant follicle continues to grow and synthesizes estradiol, progesterone, and
androgen. Estradiol stops the menstrual flow from the previous cycle, thickens the
endometrial lining, and produces thin, watery cervical mucus. FSH regulates aromatase
enzymes that induce the 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 24–36 hours after the estradiol peak and
10–16 hours after the LH peak.

• The LH surge is the most clinically useful predictor of approaching ovulation.

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, progesterone declines,
and menstruation occurs.
TREATMENT

The goal of Treatment:

✓ The prevention of pregnancy from sexual intercourse.

Additional benefits include

✓ Prevention of sexually transmitted infections [STIs].

✓ Menstrual cycle regulation.

NONPHARMACOLOGIC THERAPY
• The fertility awareness based method includes avoiding intercourse when
contraception is likely to occur. It is associated with relatively high pregnancy rates.

• Diaphragms and the cervical cap are effective barriers that should be used with
spermicide and inserted up to 6 hours before intercourse. They must be left in place for
at least 6 hours after. A diaphragm should not be left in place for more than 24 hours
due to the risk of toxic shock syndrome (TSS), while the cervical cap should not remain
in place for longer than 48 hours to reduce TSS risk. These do not protect against STIs
including human immunodeficiency virus (HIV).

• Most external condoms (also known as male condoms) are made from latex, which
is impermeable to viruses. A small percentage are made from lamb intestine, which
are not impermeable to viruses. Water soluble lubricants (ie, Astroglide and KY Jelly)
are preferred to prevent condom breakdown. Condoms with spermicides are not
recommended, as they provide no additional protection against pregnancy or STIs,
and may increase vulnerability to HIV.
• The internal condom (also known as the female condom) covers the labia and the
cervix. Its pregnancy rate is higher than with external condoms, but it protects against
many viruses, including HIV. Do not use external and internal condoms together.

• Most spermicides contain nonoxynol-9, a surfactant that destroys sperm cell walls
and blocks entry into the cervical os. They offer no protection against STIs, and when
used more than twice daily, nonoxynol-9 may increase HIV transmission.

• Phexxi is a prescription nonoxynol 9 free spermicide. It should be used within 1 hour

before each act of intercourse. It reduces vaginal pH to reduce sperm motility but
carries a risk of cystitis.

• The vaginal contraceptive sponge is available over the counter and contains
nonoxynol-9 and provides protection for 24 hours. After intercourse, it must be left in
place for at least 6 hours but no more than 24−30 hours to reduce the risk of TSS. It
should not be reused after removal.
PHARMACOLOGIC THERAPY
Hormonal Contraceptives

• Hormonal contraceptives contain a combination of estrogen and progestin or

progestin alone. They may be administered as oral contraception (OC), transdermal
patch, vaginal ring, long acting injection, subdermal implant, and intrauterine device
(IUD).

• Combined Hormonal Contraceptive (CHC) contains both estrogen and progestin

and work primarily before fertilization to prevent conception.

• Estrogens suppress FSH release (contributing to blocking the LH surge) and also
stabilize the endometrial lining and provide cycle control. Ethinyl estradiol (EE) is the
most common synthetic estrogen; however, estetrol (E4) and estradiol valerate are
also used.
• Progestins thicken cervical mucus, delay sperm transport, and induce endometrial
atrophy, while also blocking the LH surge and inhibiting ovulation. They vary in their
progestational activity and differ in their inherent estrogenic, anti-estrogenic, and
androgenic effects.
Androgenic activity depends on the presence of sex hormone (testosterone)–binding
globulin and the androgen to progesterone activity ratio. If sex hormone–binding
globulin decreases, free testosterone levels increase, and androgenic adverse effects
are more prominent.

• With perfect use, CHC efficacy is more than 99%, but with typical use, up to 7% of
individuals experience unintended pregnancy.
• Monophasic CHCs contain a constant amount of estrogen and progestin for 21 days,
while biphasic and triphasic pills contain variable amounts of estrogen and progestin
for 21 days. All are followed by a 7 day placebo phase.

• Extended cycle pills and continuous combination regimens may reduce adverse
effects and are more convenient as the number of hormone-containing pills increases
from 21 to 84 days, followed by a 7 day placebo phase, resulting in four menstrual
cycles per year.

• The progestin only “minipills” are less effective than CHCs and are associated with
irregular and unpredictable menstrual bleeding. They must be taken every day at
approximately the same time of day to maintain efficacy and are associated with more
ectopic pregnancies than other hormonal contraceptives.
• The first day start method starts on the first day of the menstrual cycle.
The Sunday start method starts on the first Sunday after the menstrual cycle starts.
The quick start method starts the day of the office visit. A second contraceptive method
should be used for 7−30 days after CHC initiation, and hormonal contraception should
resume no sooner than 5 days after the use of emergency contraception (i.e., ulipristal
acetate).

• Provided guidance about what to do if a pill is missed or if vomiting and diarrhea

occur.

• CHCs lack protection against STIs, and condoms should be used.

• The choice of an initial CHC is based on hormonal content and dose, preferred
formulation, and coexisting medical conditions.

• A complete medical examination and papanicolaou (Pap) smear are not necessary
before a CHC is prescribed. Obtain a medical history and blood pressure measurement,
and discuss the risks, benefits, and adverse medication effects before prescribing a
CHC.
• Non contraceptive benefits of CHCs include decreased menstrual cramps and
ovulatory pain; decreased menstrual blood loss; improved menstrual regularity;
decreased iron deficiency anemia; reduced risk of ovarian and endometrial cancer;
and reduced risk of ovarian cysts, ectopic pregnancy, pelvic inflammatory disease,
endometriosis, uterine fibroids, and benign breast disease.

✓ Adverse medication effects occurring in the first cycle of CHC use (eg, breakthrough
bleeding, nausea, and bloating) improve by the third cycle of use.

✓ Immediately discontinue if any warning signs referred to by the mnemonic ACHES

(Abdominal pain, Chest pain, Headaches, Eye problems, and Severe leg pain)
occur.
Transdermal Contraceptives

• Two combination contraceptives are available as a transdermal patch.

✓ Xulane delivers 35 mcg EE and 150 mcg norgestimate daily.

✓ Twirla provides 120 mcg of levonorgestrel and 30 mcg of EE daily.

✓ They are effective as CHCs in individuals weighing less than 90 kg (198 lb) or having
a BMI less than 30 kg/m2 with failure rates between 3% and 7%.

✓ Apply patch to the abdomen, buttocks, upper torso, or upper arm at the beginning
of the menstrual cycle and replace every week for 3 weeks. The fourth week is
patch free. Individuals should be counseled on the steps to follow should the patch
detach or is forgotten.

✓ Approved labeling includes a warning regarding VTE risk.

Vaginal Rings

• There are two vaginal rings available. Over a 3 week period NuvaRing releases ∼15
mcg/day of EE and 120 mcg/day of etonogestrel and Annovera releases 13 mcg of EE
and 150 mcg of segesterone acetate. On first use, the ring should be inserted on or
prior to the fifth day of the cycle, remain in place for 3 weeks, and 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. A second form of contraception should be used for the first
7 days of ring use or if the ring has been expelled for more than 3 hours for NuvaRing
or 2 hours for Annovera.

• If the Annovera is not removed after 4 weeks, no backup contraception is needed,

but 1 week should lapse before a new ring is inserted.

• If the NuvaRing is left in place for 4 weeks, a pregnancy test should be taken,
followed by new ring insertion with 7 days of nonhormonal contraception.
Injectable Progestins

• Individuals who particularly benefit from progestin only methods, including minipills,
are those who are lactating, intolerant of estrogens, and those with concomitant
medical conditions in which estrogen is not recommended.

• Injectable and implantable contraceptives are also beneficial for individuals with
adherence issues as failure rates are lower than with CHC.

• Depot medroxyprogesterone acetate (DMPA) 150 mg is administered by deep

intramuscular injection in the gluteal or deltoid muscle within 5 days of onset of
menstrual bleeding, and repeated every 12 weeks.

• Another formulation contains 104 mg of DMPA (DepoSubQ Provera 104), which is

injected subcutaneously into the thigh or abdomen. Exclude pregnancy if more than 1
week late for repeat injection of the intramuscular formulation or 2 weeks late for
repeat injection of the subcutaneous formulation. Return of fertility may be delayed
after discontinuation.
• DMPA can be given immediately postpartum in individuals not breastfeeding, and at
6 weeks postpartum if breastfeeding. The median time to conception from the first
omitted dose is 10 months.

✓ DMPA is contraindicated with a current breast cancer diagnosis and used cautiously
with a history of breast cancer, cardiovascular disease, or lupus.

✓ The most frequent adverse medication effect is menstrual irregularity, which

decreases after the first year. Breast tenderness, weight gain, and depression occur
less frequently.

✓ DMPA has a black box warning for reduced bone mineral density (BMD) but not
increased fracture risk. BMD loss seems to be greater with increasing duration of use,
and for the majority it is reversible. DMPA should not be continued beyond 2 years
unless other contraceptive methods are inadequate.
Subdermal Progestin Implants

• Etonogestrel implant (Nexplanon) is a radiopaque, 4 cm implant 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/day at the end of the 3 years of
recommended use. Efficacy exceeds 99%, but it may be less in individuals who weigh
more than 130% of their ideal body weight.

• Its contraceptive effects are quickly reversible upon removal.

• Need for backup contraception varies based on prior contraceptive use and where
in the menstrual cycle the implant is inserted. Fertility returns 30 days after removal.

✓ Irregular menstrual bleeding is common followed by headache, vaginitis, weight

gain, acne, and breast and abdominal pain. It does not appear to decrease BMD.
Fertility returns within 30 days of removal.

✓ There is potential for interactions in the presence of potent CYP450 inducers

(eg, rifampin, phenytoin, and carbamazepine)
Intrauterine Devices (IUDs)

• The contraceptive activity occurs before implantation. Endometrial suppression is

caused by progestin releasing IUDs. Efficacy rates are greater than 99% and their
contraceptive effects are reversible upon removal.

• Consideration of an IUD is appropriate in nulliparous and adolescent individuals,

given high efficacy and low complication rates. Need for backup contraception varies
based on prior contraceptive use and when in the menstrual cycle the implant is
inserted.

• The risk of pelvic inflammatory disease among users is low with no long term effects
on fertility.

• ParaGard (copper) can be left in place for 10 years. Mirena, Liletta, Skyla, and
Kyleena release levonorgestrel and must be replaced after 6 years (Mirena, Liletta, and
Kyleena) and 3 years (Skyla).
✓ Major adverse medication effects include increased menstrual blood flow and
dysmenorrhea with ParaGard, while levonorgestrel IUDs are associated with
reduced menstrual blood loss and possible amenorrhea.
Special Consideration for Contraceptive Use

Over 35 Years of Age

• Use of CHCs containing less than 50 mcg estrogen may be considered in healthy
nonsmoking individuals older than 35 years.

• CHCs are not recommended for individuals older than 35 years with migraine,
uncontrolled hypertension, smoking, or diabetes with vascular disease.

• Studies have not demonstrated an increased risk of cardiovascular disease with Low
dose CHCs in healthy, non obese individuals.

• Smoking 15 or more cigarettes per day by individuals over 35 years is a

contraindication to the use of CHCs, and progestin only methods should be considered.
Smoking

• Use of a CHC with less than 50 mcg EE should be used in individuals younger than 35
who smoke to reduce the risk of myocardial infarction (MI).

Hypertension

• CHCs, regardless of estrogen dose, can cause small increases in blood pressure
(6–8 mm Hg). Use of low dose CHCs is acceptable in those younger than 35 years with
well controlled and monitored hypertension to reduce the risk of MI and stroke.

• Individuals with a systolic blood pressure of 140−159 or a diastolic blood pressure of

90−99 mm Hg should avoid CHCs. Their use is contraindicated with blood pressures
≥160/100 mm Hg.

• Monitor potassium with potassium sparing diuretics, angiotensin converting enzyme

inhibitors, angiotensin receptor blockers, or aldosterone antagonists if also using a
product containing drospirenone.
Diabetes

• Nonsmoking individuals younger than 35 years with diabetes but no vascular disease
can safely use CHCs. Individuals with diabetes for >20 years or with vascular disease
should not use CHCs.

Dyslipidemia

• Generally, synthetic progestins decrease high density lipoprotein (HDL) and increase
low density lipoprotein (LDL). Estrogens decrease LDL but increase HDL and may
moderately increase triglycerides. Most low dose CHCs have no significant impact on
HDL, LDL, triglycerides, or total cholesterol.

• The mechanism for the increased cardiovascular disease in CHC users is believed to
be thromboembolic and thrombotic changes, not atherosclerosis.

• CHCs use in individuals with dyslipidemia as a single cardiovascular risk factor is

generally acceptable. An alternative method of contraception is recommended in
individuals with dyslipidemia and other cardiovascular risk factors.
Thromboembolism

• The risk of venous thromboembolism (VTE) in individuals using combined oral

contraceptives (COCs) is three times that of nonusers but is less than the risk of
thromboembolic events during pregnancy.

• Estrogens increase hepatic production of factors involved in the coagulation

cascade. Risk for thromboembolic events is increased in those with underlying
hypercoagulable states or with acquired conditions (eg, obesity, pregnancy,
immobility, trauma, surgery, and certain malignancies) that predispose to coagulation
abnormalities.

• COCs containing the newer progestins (eg, drospirenone, desogestrel, norgestimate)

carry a slightly increased risk of thrombosis compared to other progestins due to
unknown mechanisms.

• The transdermal patch and vaginal ring provide continuous higher exposure to
estrogen and have an increased thromboembolic risk.
• For individuals at increased risk of thromboembolism (older than 35 years, obesity,
smoking, personal or family history of venous thrombosis, prolonged immobilization),
consider low dose oral estrogen contraceptives containing older progestins or
progestin only methods.

Obesity

• COCs have lower efficacy in obesity, and low dose COCs may be especially
problematic. IUDs, implants, and DMPA have very low failure rates, and progestin only
contraceptives are considered safe in obese individuals.

• Obese individuals have increased VTE risk, and progestin only contraception may be
better for those over 35 years.
Migraine Headache

• CHCs may decrease or increase migraine frequency.

• CHCs may be considered for healthy, nonsmoking individuals (less than 35 years
old) with migraines without aura. Discuss continued use of CHC risks and benefits with
individuals developing migraines without aura.

• Individuals of any age who have migraine with aura should not use CHCs due to the
risk of stroke. individuals who develop migraines with aura while receiving CHCs
should discontinue their use and consider a progestin only option.
Breast Cancer

• There is a small increase in the relative risk of having breast cancer while CHCs are
taken and for up to 10 years following discontinuation.

• For individuals over the age of 40 or those with elevated breast cancer risk due to
family history or other factors, alternatives may be considered.

• The choice to use CHCs should not be influenced by the presence of benign breast
disease or a family history of breast cancer. For individuals with either BRCA1 or
BRCA2 mutation, CHC use is controversial, and individuals with a current or past
history of breast cancer should not use CHCs.
Systemic Lupus Erythematosus (SLE)

• COCs with less than 50 mcg EE do not increase the risk of flare in those with stable SLE
and without antiphospholipid/anticardiolipin antibodies.

• CHCs and progestin only products should be avoided in individuals with SLE and
antiphospholipid antibodies or vascular complications. The copper IUD may be the best.

• For those with SLE without antiphospholipid antibodies or vascular complications,

progestin only contraceptives or the copper IUD may be an alternative.

•A copper IUD and DMPA injection should be avoided in those with SLE and severe
thrombocytopenia.
Postpartum

• In the first 21 days postpartum (when the risk of thrombosis is higher), estrogen-
containing hormonal contraceptives should be avoided due to increased VTE risk.
Progestin only methods should be used if contraception is necessary.

• CHC should be avoided in the first 42 days postpartum in individuals with VTE risk
factors and for 30 days for those without VTE risk factors who are breastfeeding.
Drug Interactions

• Tell patients to use an alternative method of contraception if a possible medication

interaction may compromise OC efficacy.

• There is a small interaction risk with antimicrobials, and additional nonhormonal

contraceptives should be considered, especially when receiving an antimicrobial for
more than 2 months.

• Rifampin reduces the efficacy of CHCs. Additional nonhormonal contraception

should be used for at least 7−28 days after rifampin therapy.

• Phenobarbital, carbamazepine, and phenytoin potentially reduce the efficacy of

CHCs, and many anticonvulsants are known teratogens. IUDs, injectable
medroxyprogesterone, or nonhormonal options should be used instead.

• CHCs may decrease the efficacy of lamotrigine and increase seizure risk.
• Certain antiretroviral therapies and St. John’s Wort may decrease the efficacy of
CHCs.

• Monitor potassium in patients taking drospirenone and concomitant medications that

increase potassium levels or those taking strong CYP3A4 inhibitors.

Return of Fertility After Discontinuation

•There is no evidence that hormonal contraception use decreases subsequent fertility

and there is no greater chance of miscarriage or a birth defect in the first month after
discontinuation.
Emergency Contraception (EC)

• EC is used to prevent unintended pregnancy after unprotected or inadequately

protected sexual intercourse.

• FDA approved progestin only and progesterone receptor modulator products are
recommended as first line EC options. They will not disrupt the fertilized egg if
implantation has already occurred.

• Progestin only EC formulations containing one 1.5 mg tablet of levonorgestrel are

available without a prescription in the United States. They may be less effective in
individuals weighing greater than 75 kg.

• Ulipristal (Ella) is a prescription selective progesterone receptor modulator. It is taken

as a single dose of 30 mg within 120 hours (5 days) of unprotected intercourse. It is
considered non-inferior to levonorgestrel containing ECs and is not recommended in
breastfeeding individuals.
• Common adverse medication effects of EC include nausea, vomiting, and irregular
bleeding.

• Insertion of a copper IUD or prescribing higher doses of CHCs (Yuzpe method) are
other EC options.

• EC should be given within 72 hours (3 days) of unprotected intercourse, but the sooner
it is taken, the greater the efficacy. There is some evidence that it may be effective for
up to 5 days after unprotected intercourse, but in this situation ulipristal or a copper IUD
may be a better option.

• Backup nonhormonal contraceptive methods should be used after EC for at least 7

days.
Pregnancy Termination
• Medications used in early pregnancy (≤70 days) termination include mifepristone
and misoprostol. Misoprostol can be used alone or more effectively in combination
with mifepristone.

• The FDA has approved mifepristone 200 mg orally on day 1 and then misoprostol 800
mcg buccally 24–48 hours after the mifepristone dose. This regimen has a 98% efficacy
in pregnancies up to 49 days.

• Mifepristone binds progesterone receptors to block progesterone, resulting in

cervical softening and an increase in prostaglandin sensitivity, leading to contraction
stimulation. Mifepristone is usually administered orally, and prescribing is limited to
trained prescribers who also dispense the medication. It is contraindicated in patients
with bleeding disorders or those on anticoagulants. It is a major substrate for CYP3A4,
so medication interactions need to be considered.
• Misoprostol is a prostaglandin 1 analog that has good absorption when given
vaginally, buccally, or sublingually resulting in cervical ripening and contractions. Oral
administration is not recommended.

✓ Adverse medication effects of misoprostol include stomach upset, diarrhea,

headache, dizziness, and fever.

✓ Mifepristone has a boxed warning regarding infection and excessive bleeding may
occur and could be a sign of incomplete termination or other complications and
needs prompt medical attention.
EVALUATION OF THERAPEUTIC OUTCOMES

• Monitor blood pressure annually in all CHC users.

• Monitor glucose levels closely when CHCs are started or stopped in individuals with a
history of glucose intolerance or diabetes mellitus.

• Contraceptive users should have an annual exam that may include cytologic
screening, and pelvic and breast examination. Regularly evaluate for problems that
may relate to the CHCs (eg, breakthrough bleeding, amenorrhea, weight gain, and
acne). These screenings do not have to occur before prescribing hormonal
contraceptives.

• Monitor Nexplanon users annually for menstrual cycle disturbances, weight gain,
local inflammation or infection at the implant site, acne, breast tenderness,
headaches, and hair loss.
• Evaluate individuals using DMPA every 3 months for weight gain, menstrual cycle
disturbances, and fractures.

• Monitor IUD users at 1 to 3 month intervals for proper IUD positioning, changes in
menstrual bleeding patterns, and upper genital tract infection.

• Clinicians should monitor and when indicated screen for HIV and STIs. Counsel about
healthy sexual practices, including the use of condoms to prevent transmission of STIs
when necessary.
THANK YOU