The RxConsultant

Hormonal Contraceptives
2022 Volume 31 Issue 7

2 HOURS CE

Stacey Schneider, PharmD

Warda Nawaz, PharmD
 Introduction
The Bottom Line Though the prevalence of unintended pregnancies has declined in
the U.S. from 51% in 2008 to 45% in 2011, some groups tend to have
• Almost half of all pregnancies in the U.S. are higher instances of unintended pregnancy.1 These groups include
females who are:1,2
unintended, which can be prevented through
the appropriate use of prescription hormonal • 18 to 24 years old

contraceptives. • Non-Hispanic Black or African American

• Cohabiting with a partner, but not married
• Though the pill is the most common hormonal • Low-income
contraceptive method prescribed in the U.S., • Non-high school graduates
many other methods exist as well that offer the About half of these pregnancies occur in women who say they were
user personal control, autonomy, and lower using some form of contraceptive, usually from inconsistent use of
frequency of use, such as the vaginal ring and the that contraceptive.3 Preventing unintended pregnancy is beneficial
transdermal patch. for the mother and the baby, ensuring the mother is in good health
before a planned conception. If a woman does not intend to get
pregnant, she may have unhealthy habits or behaviors that could
• The most common side effects of hormonal
put the pregnancy at risk, resulting in birth defects, complications,
contraceptives include nausea, breast tenderness, or termination of the pregnancy.1 Therefore, preventing pregnancy
bloating, headache, and the most serious side at an inappropriate or unplanned time is essential to protecting the
effects include blood clots in the legs, heart, and mother and the child’s health.
brain. Pharmacists and providers should assess the need for contracep-
tives in women of reproductive age, have basic knowledge of the
• The most common drugs to interact with types of contraceptives available, and know how to appropriately
prescription hormonal contraceptives are CYP3A4 select a product based on the patient’s unique profile and health
status.
inducers, which are drugs that increase the
metabolism of estrogen and progesterone. Menstrual Cycle Overview
An understanding of the menstrual cycle is needed to understand
• Women on hormonal contraceptives should be how hormonal contraceptives work. The menstrual cycle is con-
monitored for the possibility of pregnancy and trolled by a hormonal negative and positive feedback system on
annual exams should assess for blood pressure, the hypothalamus and pituitary gland. The hypothalamus, the area
of the brain responsible for sexual motivation, releases gonado-
weight gain, changes in mood, and signs and
tropinreleasing hormone (GnRH). GnRH then stimulates the anterior
symptoms of blood clots. pituitary to release follicle-stimulating hormone (FSH) and luteinizing
hormone (LH). FSH stimulates the ovaries to develop follicles that
will develop into mature eggs, while LH stimulates ovulation of the
mature egg and development of the corpus luteum from the follicle
after ovulation. The menstrual cycle length can range from 21 to 40
days, with a median length of 28 days.4 The typical reproductive life
of a female starts around the age of 12 (range 10 to 16 years) and
ends on average at 51 years.3 Figure 1 illustrates the menstrual cycle
phases and associated fluctuations in hormone levels discussed in
detail below.

Follicular Phase (Days 1 – 14)

Both menstruation and proliferation of the uterine lining occur during
the follicular phase. The start of menstruation represents day 1 of the
menstrual cycle, during which the inner layers of the uterine lining

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Figure 1. The Menstrual Cycle
takes place two days before ovulation
through the day of ovulation.4

Luteal Phase (Day 14 – 28)

Progesterone continues to rise, secreted
by the corpus luteum. This maintains the
uterine lining, which continues to get thicker
and grow bigger in preparation for implan-
tation. High progesterone levels result in
negative feedback to the hypothalamus
decreasing LH production and ensuring
no more follicles are allowed to mature. If
no pregnancy occurs, the corpus luteum
degenerates after 9 – 11 days. Progester-
one levels then drop; no longer maintaining
the uterine lining and the menstrual cycle
begins again.4

A woman becomes pregnant when the

egg is successfully fertilized by sperm
and attaches to the uterine wall.3 When
pregnancy occurs, the corpus luteum does
not disintegrate and will continue to secrete
hormones to maintain the uterine lining
until the placenta is developed enough to
take over.4

Approaches to Contraception
Pregnancy can be prevented in sexually
are shed, causing vaginal bleeding. Men- Ovulatory Phase (Day 14)
active women by preventing the egg and
struation typically lasts 4-8 days (average of The release of the mature egg, or ovulation, sperm from meeting (e.g., barrier meth-
5 days). Estrogen and progesterone levels occurs in response to an LH surge caused ods, preventing ovulation with hormonal
are low at the beginning of this phase. by positive feedback on the pituitary by contraception) or by preventing a fertil-
Toward the end of menstruation, FSH levels high estradiol levels at the end of the fol- ized egg from implanting in the uterus
slowly increase, causing follicles in both licular phase. After the egg is released, the (e.g., intrauterine device). According to a
ovaries to grow and mature, each contain- follicle becomes the corpus luteum which contraceptive survey taken by U.S. women
ing an egg. Between days 5 – 7, only one then begins to secrete androgen, proges- between 2017 to 2019, the most common
dominant follicle will continue to mature terone, and estradiol.4 Ovulation typically methods of contraception among women
and eventually release a mature egg. This occurs 16 to 32 hours after the LH surge.6 aged 15 to 49 were female sterilization
dominant follicle produces high levels of Fertilization is most likely when intercourse (18.1%), birth control pills (14%), long-acting
estradiol, causing negative feedback on the
secretion of GnRH by the hypothalamus and ABOUT THE AUTHORS
consequently decreasing FSH production
by the pituitary.5 The drop in FSH then stops Stacey Schneider, PharmD is an adjunct professor in clinical
the growth and maturation of the remaining psychopharmacology at Saybrook University. She has practiced in the community
follicles. The increase in estradiol stops as a clinician and director of medication management services and is currently
menstruation and stimulates the thickening consulting as a medical writer.
of the uterine lining to prepare for the im- Warda Nawaz, PharmD is a freelance medical writer specializing in women’s
plantation of a fertilized egg. Estradiol also health. She has practiced as a community pharmacist for two years. She uses her
thins the cervical mucous to allow sperm to patient care experience and research background to educate professionals and
enter the uterus to fertilize the egg.4,5 create health content for consumers.

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Table 1. Failure Rates of Contraceptive
Methods 9,10 (% probability of first year failure) Mechanism of Action of Hormonal
Perfect Typical Contraceptive Agents Many types of hormonal contraceptives
Method Use Use The mechanism by which hormonal con- are designed to have a hormone-free
traceptives work to prevent pregnancy de- dosing interval either by including placebo
COC and POP < 1% 7% pills in the cycle pack or by removing the
pends on whether they contain a proges-
Norelgestromin/Ethinyl < 1% 7% delivery device (e.g., ring, patch) for a
terone component only or a combination
estradiol TDP period of time. This progestin-free period
of estrogen and progesterone components.
n/a 3% In general, hormonal contraceptives work causes shedding of the uterine lining, or
Levonorgestrel/Ethinyl
by taking advantage of the negative feed- withdrawal bleeding, imitating the natural
estradiol TDP
back loop of the hypothalamus to prevent menstrual cycle.11
Etonogestrel/ethinyl <1 % 7%
estradiol VR ovulation.
Combined Hormonal
n/a 3% Estrogen Contraceptives (CHC)
Segesterone/ethinyl
estradiol VR Combined hormonal contraceptives con-
Estrogens for hormonal contraception
tain both estrogen and progestin active
DMPA < 1% 4% include ethinyl estradiol, the most common,
components. In these products, estrogen
mestranol, estradiol valerate, and esterol.
Transdermal Implant < 1% <1 % and progestin work synergistically to pre-
Estrogens are highly lipophilic, lending to
IUD < 1% < 1% vent ovulation by combining mechanisms
good absorption with oral, injectable, and
of action.8 They are available in pill, patch,
Abbreviations: COC, combined oral contraceptive, POP, topical administration.10 Estrogen prevents
progestin only pill; TDP, transdermal patch; VR, vaginal ring; and ring dosage forms.
DMPA, depot medroxyprogesterone acetate; IUD, intrauter-
pregnancy by providing sustained negative
ine device feedback to the hypothalamus, thus inhib- Combined Oral Contraceptives (COC)
iting FSH and preventing the development
reversible contraceptives, including IUDs Combined oral contraceptives, often
of mature follicles and eggs.4,11
and contraceptive implants (10.4%), and called “the pill,” are hormonal pills contain-
male condoms (8.4%).7 Progestin ing estrogen and progestin components.
There are many choices available for COC.
Regardless of contraceptive choice, each A dozen different types of synthetic pro-
The following are characteristics that dis-
option has advantages and disadvantages, gesterones, or progestins, are used in hor-
tinguish COC products from each other:
depending on the woman’s preference, monal contraceptives. Sustained progestin
health status, side effect profile, risk of levels prevent pregnancy by providing neg- Dose of ethinyl estradiol – Ethinyl estra-
drug interactions, ease of use, frequency of ative feedback to the hypothalamus, thus diol comes as a low dose (10-40 mcg) or
use, and route of administration. This issue inhibiting LH and preventing the release of high dose product (50 mcg or higher). The
will discuss the mechanisms of hormonal the mature egg from the ovary.11 Proges- 20 mcg dose can be used as a starting
contraceptives, efficacy rates, and the terone undergoes extensive first-pass dose in new patients; however, the lower
nuances of various formulations. metabolism, so it can only be administered estrogen levels may cause spotting or
as a vaginal gel, intrauterine device (IUD), erratic withdrawal bleeding. The 20-25
Efficacy Rates of Hormonal or injectable formulation; however, hepatic mcg dose is given to people who do
Contraceptives metabolism is slower with progestins com- not tolerate the 30 or 35 mcg dose due
Failure rates of hormonal contraceptives pared with progesterone allowing for their to side effects including bloating breast
are provided for perfect use (the woman oral administration.12 Progestins also work tenderness, and nausea.11,13
used the contraceptive exactly as directed) by thickening the cervical mucus to prevent
sperm entry, slowing egg movement Type of progestin – Progestins vary in
and typical usage (combines perfect use
through the fallopian tubes, and thinning their potency, androgenicity, and side
failure rate plus typical user ability to follow
the uterine lining to make it less favorable effects. In general, the newer progestins
directions correctly and consistently). The
for implantation of a fertilized egg.10 such as desogestrel, gestodene, and
perfect use rate shows how effective a
norgestimate have fewer androgenic
contraceptive method can be, and the typi-
Depending on the product type and when properties and fewer side effects than
cal use rate reflects users who occasionally
in the cycle it is started, backup contracep- earlier generation progestins such as
forget a dose through those who rarely
tion, such as abstinence from intercourse levonorgestrel and norethindrone.12
take a dose.8,9 Table 1 shows the efficacy
or male condoms with spermicide, may Drospirenone exhibits anti-androgenic and
rates of hormonal contraceptives.
be used until ovulation is suppressed to diuretic properties but has a higher risk of
prevent pregnancy.4 clot formation than other progestins.13

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Table 2. Examples of Mono and Multiphasic Oral Contraceptives14
al-related disorders such as dysmenorrhea
(painful bleeding), endometriosis, premen-
Ethinyl
Oral estradiol (ug) Progestin (mg) U.S. Brand Names* strual syndrome, and menorrhagia (exces-
sive menstrual bleeding).15 A 2018 study
Monophasic 20 drospirenone 3 BeyazTM, Loryna TM, Nikki TM, Yaz® found no clinically significant risk of blood
levonorgestrel 0.1 Larissa TM, Lessina®, Lutera TM, Sronyx® clots with continuous cycle versus cyclic
birth control pills.16 Examples of monthly,
norethindrone 1 Junel TM 1/20, Larin TM Fe, Loestrin 24
Fe®, Microgestin® quarterly, and yearly formulations are sum-
marized in Table 3.
30 drospirenone 3 Ocella TM, Safyral TM, Tydemy TM,
Yasmin® Patients should be asked if they prefer
norethindrone 1.5 Loestrin Fe, Microgestin Fe, Junel
® ® TM regular monthly withdrawal bleeding (21
active/7 placebo or 24 active/4 placebo for-
35 norgestimate 0.25 Sprintec®, Ortho-Cyclin®, MonoNessa® mulations), bleeding every three months (84
active/7 placebo formulations), or no with-
norethindrone 1 Nortrel®, CyclafemTM
drawal bleeding (365 active, no placebo).
Biphasic 20, 0, 10 desogestrel Azurette®, Mircette®
0.15, 0, 0 Number and type of placebo pills – For
women who choose to have a withdrawal
10, 10 norethindrone 1, 0 Lo Loestrin® Fe
bleed, the length of withdrawal bleeding is
Triphasic 30, 40, 30 levonorgestrel Levonest TM, Trivora® determined by the number of placebo pills
0.05, 0.075, 0.125 contained in the product. Most hormonal
35, 35, 35 norgestimate Ortho Tri-Cyclen®, Tri-Previfem®, contraceptive products come with either 4
0.18, 0.215, 0.25 Tri-Sprintec® or 7 days of placebo pills.11 The seven day
hormone-free interval has no biological
Quadriphasic estradiol dienogest (mg) NataziaTM
basis and was initially devised to mimic
valerate (mg) 0, 2, 3, 0
monthly menstrual bleeding.15 Some prod-
3, 2, 2, 1
ucts have placebo pills containing folate
(BeyazTM, SafyralTM) or iron (Lo Loestrin® Fe).
, all tablets contain levomefolate calcium; Fe, placebo tablets contain ferrous fumarate
Fa
Products with folate benefit women who
want to prevent neural tube defects should
Monophasic vs. Multiphasic – There is no monal fluctuations in the menstrual cycle.
pregnancy occur while taking the pill. Iron
difference in efficacy between mono- and Multiphasic pills may have two (biphasic),
pills are added to products to reduce the
multiphasic hormonal contraceptives, they three (triphasic), or four (quadriphasic) sets
risk of anemia and iron deficiency.20 Con-
all have similar contraceptive effectiveness of estrogen and progestin doses followed
sider these products in women with heavy
if used correctly and consistently.11 Examples by placebo. Multiphasic pills must be taken
menstrual bleeding and associated anemia.
of monophasic and multiphasic pills are sequentially; they may also result in more
listed in Table 2. mood changes than monophasic products.11 Advantages of COC include: 15
Monophasic products have the same Cycle preference – The frequency of • Ease and convenience of use compared
dose of estrogen and progestin in all the withdrawal bleeding is determined by how to implants or insertion methods
active pills, followed by placebo. They are often placebo pills are taken. It is generally • Ability to easily track daily pill intake
easy to take because the active pills are considered safe for patients to take an ex- using days of the week on the package
not required to be taken in a sequential tended cycle (withdrawal bleed every three • Ability to personalize treatment based on
order. Monophasic products can be used months) or continuous cycle (no withdrawal the patient’s cycle preference and desire
for withdrawal bleeding
for extended or continuous cycle regimens bleed) over the traditional cyclic monthly
by skipping placebo pills and starting a new withdrawal bleed regimen.15 A systematic Disadvantages of COC include: 4,8,13,21,22-24
pack.11 review in 2014 found that these regimens
• Daily regimen which could hinder
have similar efficacy for contraception. adherence in some patients
Multiphasic pills are split into different
Extended cycle and continuous cycle regi-
phases, with each pill phase containing • Dependency on the user to be effective
mens should be recommended to women compared to other methods (IUD,
different levels of estrogen and progestin
who want to avoid menstrual bleeding for implants, injectable)
that are meant to closely mimic the hor-
personal reasons or to help treat menstru-

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 Table 3. Traditional Cycle Regimens vs. Extended and Continuous Cycle Regimens14
• Systemic absorption, resulting in nausea
or vomiting, and other unwanted side COC Regimens Example U.S. Brand Names
effects
Traditional Junel TM Fe 1/20, LarinTM Fe 1/20,
• Metabolism through the liver, resulting in 21-day (21 active pills, 7 placebo pills) Loestrin® Fe 1/20, LuteraTM, Microges-
the production of blood clotting factors, Monthly 7-day bleeding
and risk for drug-drug interactions with tin® Fe 1/20, Portia®, Sprintec®, Tri Lo
CYP3A4 inducers Sprintec®
• Chance of pregnancy if the patient Mini Continuous Cycle 24-Day Beyaz TM, Nikki TM, Minastrin® 24 Fe,
misses two or more pills (24 active pills, 4 placebo pills) Yaz®
• Estrogen component may be unfavorable For shorter periods
in women who cannot tolerate it or are at Mini Continuous Cycle 26-Day Lo Loestrin® Fe
risk of clotting
(24 combo* pills, 2 estrogen-only pills, 2 iron
Initiation & Administration pills)
For shorter, lighter periods
COCs can be started right away if it is
known that the patient is not pregnant. No Extended Cycle 91-Day Ashlyna, LoSeasonique®, Seaso-
additional contraceptive method is needed (84 combo* pills, 7 estrogen-only pills) nale®, Seasonique®, Quasense
if started within the first five days of men- For periods every 3 months
strual bleeding. If started more than five Continuous Cycle 365-Day AmethystTM
days after the onset of menstrual bleeding, (28 active pills, no placebo pills)
the patient must abstain from sexual inter- For very light or no periods all year
course or use a backup method for the next *Combo pills refer to the combination of progesterone and estrogen ingredients
seven days to prevent pregnancy.8 COCs
must be taken by mouth once a day, at the Advantages of transdermal patches: 4,25 Dosing
same time each day, for best efficacy.4,10 • Easily reversible hormonal contraception XulaneTM delivers 150 mcg norelgestromin
compared to implants, IUDs, or injection and 35 mcg ethinyl estradiol daily. TwirlaTM
It is not advisable to start COCs in women
three weeks postpartum because of the risk • Avoidance of first-pass metabolism delivers of 120 mcg levonorgestrel and
and enzymatic degradation within the 30 mcg ethinyl estradiol daily.26,27 TwirlaTM
of decreased milk production and increased
gastrointestinal tract
risk of developing venous thromboembo- has a lower dose of ethinyl estradiol than
lism (VTE) or blood clots in veins.8,13 If the • Avoidance of first-pass induction of XulaneTM (30 mcg vs 35 mcg), and contains
hepatic protein synthesis, especially of
patient is not breastfeeding, use clinical extrinsic clotting factors a different progestin.27
judgment to determine eligibility to start
• Weekly administration versus daily Initiation and administration
therapy. Avoid COCs in women 3-6 weeks administration of oral contraceptives
after delivery because of concerns of devel- Patches should be started within 24 hours
• Continuous, sustained release of the
oping VTE.8 drug resulting in steady hormone levels of day one of the menstrual cycle. Another
in the blood option is to start on the first day of Sunday
Transdermal Patch after the menstrual period begins. With the
The estrogen and progestin in transdermal Disadvantages of transdermal patches: second option, a non-hormonal backup
21,26,27
patches are absorbed through the skin method must be used for seven days. The
directly into the systemic circulation. They • Local site reactions, including skin rash patches must not be cut, damaged, or al-
are a convenient weekly CHC option for • Lack of efficacy in overweight or obese tered in size, this will affect how the patch
women who cannot remember or do not women (body mass index [BMI] ≥ 30 works. Application sites include clean, dry
want to take birth control pills daily.25 The kg/m2 for TwirlaTM) and (≥ 198 lbs for skin of the abdomen, upper outer arm, but-
XulaneTM) tocks, and upper torso (excluding breasts)
two contraceptive patches available in the
U.S. are TwirlaTM and XulaneTM. Transdermal • Higher overall estrogen exposure and should not be placed in an area where
compared to COCs, could result in a tight clothing may rub it, such as the
patches are an excellent option for women higher risk of blood clots
with a healthy weight, who possess good waistline. Each patch is worn for seven days
tolerance to estrogen, and a low risk for • Slightly higher rates of breast tenderness during weeks 1 - 3 of the cycle, then re-
compared to COCs
blood clots.25-27 moved, discarded, and replaced with a new
patch at a new application site. No patch is
worn during week 4 of the cycle. The patch

6
free week 4 is when withdrawal bleeding Disadvantages of vaginal rings: 28-30,33 these may interfere with the ring place-
is expected to occur. If the patch falls off, it • Irritation of vagina or cervix ment). No backup is needed if starting with-
should be reapplied as soon as possible. If in the first five days of 1st-trimester abortion
• Ring slipping out (during intercourse or
the patch has been off for a day or more while straining) or causing discomfort. or miscarriage. Do not start therapy in
the woman is not protected from pregnancy patients sooner than four weeks following
• Vaginal discharge
and should use a non-hormonal backup a 2nd-trimester abortion or miscarriage, as
method for seven days. A new patch should • Feeling the ring during intercourse there is an increased risk of thromboembo-
be started for a new 4-week cycle.26,27 lism. Avoid initiating sooner than four weeks
Dosing
postpartum in women who are not breast-
Vaginal Ring NuvaRing® is 54 mm in overall diameter, feeding. If no period has started, consider
Vaginal rings are small (about 5.5 cm in with a cross-sectional diameter of 4 mm. the possibility that ovulation had occurred
diameter) and flexible rings inserted into It releases an average of 0.12 mg/day of before initiating therapy. 29,30
the vagina that continually release estrogen etonogestrel and 0.015 mg/day of ethinyl
estradiol over three weeks. One ring is To insert, advise the patient to take the ring
and progestin for absorption into systemic
inserted into the vagina each month and out of its packaging, compress the sides,
circulation through the vaginal lining. The
remains in place for weeks 1 - 3 and is and insert it as far up in the vagina as pos-
site in the vagina where the ring is placed
removed during week 4 for a hormone-free sible so it is not felt during intercourse and
does not matter, as any part of the vagi-
interval. The system provides contraception does not inadvertently fall out. The woman
na has equal capability of absorbing the
for one cycle and is discarded after removal. may choose any comfortable position for
hormones. After an initial spike in hormone
A new ring is inserted each month.29 insertion: squatting, lying down, or with a
levels upon first insertion, there are steady
leg raised. The exact placement of the ring
plasma levels of estrogen and progestin AnnoveraTM is 56 mm in overall diameter, is not important for effectiveness.29,30
while the ring is inserted. This contrasts with a cross-sectional diameter of 8.4 mm.
with the daily fluctuation in hormone levels It releases an average of 0.15 mg/day of The AnnoveraTM ring should be cleaned with
associated with oral administration.28 The segesterone acetate and 0.013 mg/day mild soap and warm water and stored in a
two contraceptive rings available in the of ethinyl estradiol over three weeks. The case during the week 4 dose-free interval.30
United States market are etonogestrel and system provides contraception for thirteen The patient may skip the ring-free week
ethinyl estradiol (NuvaRing®) and segester- cycles and is reused monthly for one year.30 for an extended cycle to avoid menstrual
one acetate and ethinyl estradiol (Annover- bleeding, but this is not FDA-approved.34
aTM). See Table 4 online for product details. The next cycle for both products is started
by inserting the vaginal ring one week after NuvaRing® Prolonged Use
Advantages of vaginal rings: 28,31-33 the previous ring was removed, on the If the ring is kept in for up to 4 weeks,
• Ease of use without remembering to take same day of the week, and at approximate- the woman will be protected. Advise the
daily pills or weekly patch changes ly the same time of day, even if menstrual patient to remove the ring for one week,
then insert a new one. If the ring is left in
• Good cycle control bleeding is still occurring. 29,30 for more than four weeks advise the patient
to remove the ring and rule out pregnancy.
• Steady and constant hormonal release
Initiation & Administration If pregnancy is ruled out, the ring may
• Avoidance of first-pass metabolism be restarted, and an additional form of
The ring should be started between days
and enzymatic degradation within the contraception should be used until a new
gastrointestinal tract 1 to 5 of the menstrual cycle. If started on NuvaRing® is used continuously for seven
day 1 no backup method is needed. If the days.219
• Flexibility in the start and stop times
patient starts on days 2-5 of the menstrual
• Use of lowest dose of ethinyl estradiol period, a non-hormonal backup method AnnoveraTM Prolonged Use
should be used every time intercourse If the ring is left in for longer than 21 days,
• High effectiveness the recommendation is to remove it for
occurs for the first seven days while the ring seven days, then re-insert and resume the
AnnoveraTM offers an additional advantage
is in place (advise patients to avoid female 21 days in/7 days out cycle.30
to NuvaRing® because it does not need to
condoms, sponges, diaphragms, caps, as
be refrigerated and one ring can be used
for 13 cycles without the need for monthly
refills at the pharmacy. Active Learning Question 1:
What are some reasons the ring or patch would be preferred over the pill for a woman
starting on a combined hormonal contracptive?

7
Progestin-only Hormonal Table 5 contains a summary and compari- side effects such as VTE compared to
Contraceptives son between combined oral contraceptive COCs
Progestin-only hormonal contraceptives rely pills and progestin-only pills and when they • Drosperinone containing POP (SlyndTM),
on the ability of progesterone to suppress are preferred clinically. has an advantage over norethindrone
the LH surge and therefore ovulation, in products because it offers a more flexible
Progestin Only Pills (POP) missed pill window and predictable
addition to changes to the cervical mucous, bleeding pattern during placebo days
sperm transport in the fallopian tubes, and Progestin-only pills, or “minipills,” contain
thinning of the uterine lining to prevent only progestin and no active estrogen ingre- Disadvantages of POP: 24,36,37
pregnancy without the synergistic FSH dient.8,10 Norethindrone and drospirenone • Possible erratic menstrual bleeding
suppression estrogen provides in CHC.11 are the main progestins available in POPs.11
• Narrow ‘missed pill’ window (3 hours)
Progestin-only hormonal contraceptives are They work by suppressing ovulation and pe- resulting in adherence issues
available as oral pills, subcutaneous depot, ripherally by thickening the cervical mucus
• Not likely to be effective for women with
subdermal implant, and intrauterine devices to impair sperm penetration.10,12 Because epilepsy who take CYP 3A4 inducers due
(IUD).8 Progestin-only hormonal contra- of the low doses of progestin in norethin- to extremely low progesterone dose
ceptives should be considered in patients drone-containing POPs, there is less reliable
who are not candidates for combination suppression of ovulation compared to a Dosing
oral contraceptives. These include women relatively higher dose in the drospirenone
Like COCs, POPs must be taken at the
who cannot take estrogen due to estrogen product.11 same time every day continuously between
intolerance (e.g., have a history of estro- pill packs.38 There are no placebo days
gen-related headache, breast tenderness, Advantages of POP: 24,36,37
with norethindrone POPs. Because of this,
or nausea), women who are postpartum • Favorable side effect profile compared norethindrone pills require a stricter dosing
breastfeeding, have risks associated with with CHC schedule than drospirenone-only and COCs.
heart disease, blood clots, patients with • Ease and convenience of use These tablets must be taken within the same
diabetes, and smokers 35 and older.35 • Reduction of estrogen-related serious 3 hours every day to work properly. If a pill
is more than 3 hours
late, this can result in a
Table 5. Prescribing preferences for oral contraceptives in women with various health factors30
chance of pregnancy.38
Patient Health A newer drospire-
Factor COC POP none-only pill (SlyndTM)
containing twenty four
High blood Not recommended in poorly controlled blood Preferred in patients with poorly active and four placebo
pressure pressure OR well-controlled BP + heart disease risk controlled BP pills, should also be
factors taken once daily, but
High choles- Not recommended in patients with LDL-C >160, or Preferred in patients with high cho- doses can be delayed
terol multiple heart disease risk factors lesterol up to 24 hours without
Diabetes May be used in type I & II diabetic patients aged Preferred in patients with history of compromising contra-
< 35 years, who have no complications, and are diabetes and/or diabetic complica- ception. Withdrawal
nonsmokers tions including cardiovascular disease bleeding is expected to
Smoking Not recommended in women who smoke aged >35 Preferred in smokers > 35 years occur on the last four
years placebo days.36 See
Table 6 online for POP
Obesity Not recommended in women with BMI > 30 kg/m2 Preferred in obese women product summary.

Age >35 years May be used in healthy, non-smoking women aged > Preferred in women who are >35 Initiation &
35 years years Administration
Postpartum, Not recommended; results in reduced milk produc- < 6 weeks postpartum: may be Norethindrone POPs
breastfeeding tion and lactation duration used in women without risk to infant should be initiated
(weigh risk vs. benefit) whenever the patient
Migraine with Avoid use when possible; may increase risk of stroke Preferred in women with migraine is known to not be
aura or MI; may worsen headaches due to ethinyl estradiol headaches pregnant or on the first
BP: blood pressure; LDL-C: low density lipoprotein cholesterol; MI: myocardial infarction

8
day of the menstrual cycle. A non-hormonal • The injection of DMPA will require a visit up to 3 years
backup method is required for the first 48 to a clinician, which may be a barrier for
those with limited access/time for an • Typical use with the progestin implant
hours of therapy if not started on day one. in-person office visit and may result in results in lower failure rates than COCs,
Women who are six weeks postpartum can additional costs. vaginal rings, and transdermal patch,
start right away if breastfeeding or three
In 2021, the Centers for Disease Control and about the same as IUDs (<1%)
weeks postpartum if partially breastfeeding
and formula feeding their infant. POPs can and Prevention (CDC) adopted the World • Return to fertility can be expected in
also be started the following day after a Health Organization (WHO) recommenda- 1-2 weeks after discontinuation of the
miscarriage or an abortion.38 tions for the availability self-administered implant, making this a good contracep-
subcutaneous DMPA to remove this barrier, tive choice for women who desire to
The drosperinone (SlyndTM) package insert but emphasized that both provider- and get pregnant in the near future.
recommends a day one start which does self-administered approaches should be
not require the use of backup contracep- available.43 Disadvantages of the implant:45
tion.36
• Less effective in women who are
Initiation & Administration
Subcutaneous Depot obese
For women who are not using a hormonal
Depot-medroxyprogesterone acetate contraceptive, the first dose can be given at • The effectiveness of the implant has
(DMPA) is a long-acting injectable proges- any time during the menstrual cycle if preg- not been studied in women more than
tin only hormonal contraceptive similar in nancy is ruled out. If the administration is ≤7 30% overweight
structure to naturally occurring progester- days from day 1, no additional contraception
one. It is injected either intramuscularly (IM) is needed. If it has been >7 days since day Initiation & Administration
or subcutaneously (SQ) every three months. 1, abstinence from sexual intercourse or The implant should be inserted during days
The subcutaneous formulation (Depo-SubQ use of an other non-hormonal contracep- 1 through 5 of menstruation if a patient is
Provera 104®) can be self-administered by tive method for seven days following the not using a hormonal contraceptive, even
the patient while he intramuscular formu- injection is recommended.41 If switching if the patient is still menstruating. A barrier
lation (Depo-Provera® Contraceptive Injec- from another form of contraception, refer to method of contraception should be used
tion) must be administered by a healthcare Table 8 online. for the first seven days after insertion if
professional.42,43 deviating from the recommended timing
Transdermal Implant of insertion. If pregnancy is a possibility, a
Use beyond two years is not recommended
unless other options are unavailable due to The progestin-only contraceptive implant pregnancy test should be performed before
the risk of loss of bone mineral density.41,42 (Nexplanon®) is a thin, 4-cm flexible insertion.46 If switching from another form of
Table 7 online lists specific depot-medroxy- plastic latex-free rod containing the contraception, refer to Table 10 online.
progesterone acetate product details. progestin etonogestrel.45 It is a long-acting,
Due to the risk of thromboembolism asso-
reversible contraceptive inserted under the
ciated with pregnancy and the immediate
Advantages of DMPA include: 4,41 skin of the inner upper arm by a healthcare
postpartum period, the manufacturer does
• Every three month administration professional. Table 9 online lists specific
not recommend inserting the implant <21
is advantageous for women with product details, including dosing. Following
adherence issues days postpartum.45 However, available
the removal of the implant, hormone levels
guidelines state that progestin-only
• Typical use results in lower failure rates decrease rapidly and are less than the level
implants may be inserted at any time if
versus COCs, vaginal rings, and the of detection within one week.45,46
transdermal patch it is reasonably certain the patient is not
Advantages of the implant: 4,45 pregnant.46
• Women who are not breastfeeding,
but require contraception can receive • Convenient dosing in women with
DMPA immediately postpartum, unlike Intrauterine devices (IUD)
contraception methods containing adherence issues
An intrauterine device (IUD) is a small
estrogen. T-shaped device inserted into the uterus
• Protective effect against pregnancy for
Disadvantages of DMPA include: 41
• In a woman who would like to conceive
in the near future, DMPA is not a good Active Learning Question 2:
choice since the return to fertility is In what women would a progestin-only hormonal contraceptive be a better choice
generally around ten months from
discontinuation. than a combined hormonal contraceptive?

9
by a healthcare professional that acts as a Levonorgestrel IUD Initiation & tives (estrogen and progestin containing
long-term contraceptive method. Depend- Administration products) require seven days to suppress
ing on the product, an IUD can be kept in To initiate therapy in patients not currently ovulation.4 When active doses of CHC
place for up to 10 years. Four levonorge- using a hormonal contraceptive, the IUD are missed, sexual intercourse should be
strel-releasing IUDs are available in various may be inserted at any time during the avoided or a backup contraceptive should
strengths, in addition to a non-hormone menstrual cycle once it is determined that be used for seven days.4 Consult individual
IUD made of copper.4 No IUD devices have the patient is not pregnant. Backup contra- product package inserts for detailed missed
a generic alternative. Release rates for all ception is not needed if insertion is within 7 dose instructions.
hormone-releasing IUDs are higher initially, days of onset of menstruation. If insertion
then decrease over time. Table 11 online Common Side Effects of Hormonal
occurs 7 days after menstrual bleeding
lists specific product details. Contraceptives
starts, a backup method of contraception
must be used for 7 days. When it is time for Nausea, bloating, and breakthrough bleed-
Advantages of IUDs include:4,52-55 ing are common side effects experienced
a replacement, the IUD may be removed
• Highest efficacy rate in preventing and replaced with a new device at any time by women when hormonal contraceptives
pregnancy (<1% with typical use) are initiated. Women should be reassured
during the menstrual cycle if the patient is
• Beneficial in patients with adherence not pregnant.53 For patients switching from that these side effects typically resolve
issues after about three months of use.23 Table 14
a different contraceptive to the levonorge-
• Fertility usually returns after strel IUD refer to Table 12 online. shows the common side effects of estrogen
approximately two menstrual cycles and and progestin excess and deficiency in
may be beneficial in women who desire women using combined hormonal contra-
pregnancy in the relatively near future Copper IUD Initiation & Administration
ceptives. When one of these side effect is
To initiate therapy in patients not currently
identified, the contraceptive product can
using a hormonal contraceptive, the copper
be adjusted accordingly to address the
IUD may be inserted at any time during
symptom.23
the menstrual cycle if the patient is not
pregnant. When it is time to replace the IUD, Weight gain is most associated with DMPA
a new one may be inserted immediately with an average gain of 11.2 lb over three
after the previous IUD is removed.47,54 For years. Weight gain does not seem to be a
patients switching from a different contra- significant issue for women on CHC, and
ceptive to the copper IUD refer to Table 13 there is no difference in weight gain be-
online. tween available COC products.23,56

Headache is a common side effect report-

Missed Doses of Hormonal ed by women using hormonal contraception
• May be inserted immediately postpartum Contraceptives
regardless of breastfeeding status regardless of the type.57 Headache is also
Norethindrone-only products require 48 common in the general population and
• No drug interactions with the copper IUD
hours to suppress ovulation. When active evidence linking hormonal contraceptives
Disadvantages of IUDs include:47-51 tablets are missed, sexual intercourse to headaches is lacking.58 Headache is
• Placement and removal require an office should be avoided or a backup method of most common during the first cycle and in
visit to a clinician who has been trained contraception should be
with IUD placement and may prove to used for 48 hours after
be a barrier for women who do not have restarting.4 If more than
access to these resources.
one active pill from a dro-
• Can perforate the uterus, be expelled, or spirenone-only product is
become displaced, which may require
medical attention or surgical intervention missed, sexual inter-
course should be avoided,
• Prolonged bleeding, spotting, and
cramping may occur especially during or a backup method of
the first few weeks after insertion. contraception should be
used for seven days.36
• Risk of uterine perforation is higher if the
IUD is placed within 6 weeks of giving Generally, combined
birth or if breastfeeding
hormonal contracep-

10
Table 14. Common Side Effects of Combined Hormonal Contraceptives4,23
with VTE, thrombophilia, age 35 years or
Excess Deficiency older, smoking, obesity, cancer, prolonged
Estrogen Nausea/Vomiting Early cycle spotting immobilization) who have multiple risk
Early cycle breakthrough bleeding factors for atherosclerotic cardiovascular
Bloating
Amenorrhea disease, hypertension, history of ischemic
Hypertension Vaginal dryness heart disease or stroke, migraine with
Migraine headache
aura, nephropathy, retinopathy, neuropathy,
Breast tenderness vascular disease, and severe liver disease,
Decreased libido should be carefully considered.60
Weight gain
Heavy withdrawal bleed Progestin Only
Progestin Acne Late cycle spotting Ectopic pregnancy
Increased appetite Late cycle breakthrough bleeding
Weight gain Amenorrhea The chance of developing pregnancy
Fatigue Heavy withdrawal bleed outside the uterus is higher in women using
Hypertension progestin only hormonal contraception
Depression compared with women using combined
Hirsutism
hormonal contraceptives or condoms.
Vaginal candidiasis
Healthcare professionals should monitor
for ectopic pregnancy if a woman becomes
women aged 35 and older.57 There is no skin are reported side effects of pro-
pregnant or complains of lower abdominal
evidence that contraceptive type, estrogen, gestin-only hormonal contraceptives but
pain while taking a progestin-only pill.61
or progestin has an effect on headache. An there is no evidence to show this is the
extended cycle or continuous use regimen cause. Progestins that are more andro- Ovarian/Follicular cysts
may be attempted in women who expe- genic (levonorgestel, norgestrel) may
If follicular development occurs during
rience new onset headache during the contribute to these side effects.23,56 CHC
contraceptive therapy, the follicles may
hormone free placebo period when using are used to treat acne and hirsutism and
not shrink fast enough, resulting in growth
CHCs.23,58 are an option for women experiencing
beyond the size it would obtain in a normal
these side effects if they are able to take
Irregular Bleeding is the most common cycle. These “cysts” can spontaneously
a CHC.23
adverse effect of hormonal contracep- disappear, stay asymptomatic, or they may
tives and can be managed by adjusting Serious Side Effects of Hormonal burst, requiring surgical intervention.38
the levels of estrogen and progestin if Contraceptives Offer alternative contraception to women
it continues for more than 3 – 6 months concerned about developing follicular cysts
after initiation.23 Early cycle breakthrough Cardiovascular or experiencing symptoms like pain associ-
bleeding can be managed by increas- The cardiovascular side effects of hor- ated with cysts.
ing the dose of estrogen and late cycle monal contraceptives are thought to be
breakthrough bleeding can be managed by related to the estrogen component of Side Effects Related to Hormonal
increasing the progestin dose.8 Progestin CHCs.59 However, the progestin dro- Contraceptive Dosage Forms
only contraceptives and CHC with less than spirenone also has a higher risk of clot
In addition to side effects caused by
20 mcg ethinyl estradiol are most likely to formation than other progestins.6 CHCs active ingredients, there are also side
cause irregular bleeding. Although POPs may alter lipids, increase blood pressure, effects caused by some dosage forms
help avoid estrogen-related side effects and increase the risk of thrombosis. themselves Figure 2 describes the side
such as nausea, bloating, headache, and Women are at higher risk for deep vein effects caused by the patch, ring, implant,
even blood clots, they do not offer good thrombosis or pulmonary embolism DMPA, and IUD dosage forms.
regularity of menstrual bleeding.10,24 The during childbearing age and when
most common complaint from women using exposed to reproductive risk factors such
Contraindications
progestin only hormonal contraception is as pregnancy, hormonal contraception, or
irregular bleeding patterns such as spotting, hormone replacement therapy.59 Women Combined Hormonal Contraceptives
prolonged bleeding, or amenorrhea (ab- with a history of VTE who are not on A thorough personal history, current health
sence of bleeding).24 anticoagulation should not use CHC. The status, and individual risk factors should be
risks and benefits of CHC in women with obtained to determine contraindications to
Skin changes like acne, hirsutism, and oily high risk for VTE (e.g., first degree relative
11
Figure 2. Hormonal Contraceptive Dosage Form Side Effects
bolic disorders, and undiagnosed abnormal
Patch Local reaction at application site (bumps, redness, change in skin genital bleeding.46
color, rash, dryness, pain swelling)
Intrauterine Devices:
Ring Vaginal discomfort, foreign body sensation, device expulsion, coital
problems Both the levonorgestrel and copper IUDs
are contraindicated in pregnancy, emergen-
Implant Insertion and removal pain, numbness/tingling of the skin, cy contraception, congenital or acquired
bleeding from insertion site, hematoma, scarring, infection uterine anomaly, history of or current pelvic
inflammatory disease, postpartum endome-
DMPA Tenderness or a nodule at the injection site tritis, infected abortion within the past three
months, uterine or cervical malignancy, low-
IUD Although concerns about pain upon insertion of an IUD are common, er genital tract infections, uterine bleeding
insertion pain is minimal and not prolonged in most patients. NSAIDs or of unknown etiology.47-51
acetaminophen may be helpful if needed. The risk of infection upon IUD
The levonorgestrel IUD is also contraindicat-
insertion is minimal, therefore it is not recommended to prophylactically treat
with antibiotics.48 ed in acute hepatic disease, hepatic tumors,
breast cancer, or other hormone-sensitive
hormonal contraceptive use. Since hormon- • Jaundice, or yellowing of the skin due to cancer.53,48-51 The copper IUD is contraindi-
al contraceptives can lead to cardiovascular, liver disease cated in Wilson disease (a genetic disease
thromboembolic, and malignant disease, where excess copper builds up in the
the presence or history are contraindica- Patch Contraindications:26,27 body).47,54
tions for combination hormonal contracep- Absolute contraindications of the transder-
Monitoring
tive use.4,10,11 mal patches include:
All women on hormonal contraception
• BMI ≥ 30 kg/m2 should receive an annual exam, including
Absolute contraindications: 4,10,62

• Women ≥ 35 years who smoke heavily • Use of Hepatitis C drugs containing blood pressure screening and pelvic and
(>15 cigarettes/day) ombitasvir/paritaprevir/ritonavir, with breast exams. When indicated, screenings
or without dasabuvir
for sexually transmitted infections (STI) and
• History, presence, or high risk of venous
thromboembolism, or blood clots in veins Progestin Only Hormonal HIV should be done. Adherence, changes in
(VTE) Contraceptives4,38,41,42 blood pressure, migraines, venous throm-
• Known or suspected pregnancy • Presence of undiagnosed vaginal boembolism risk, body mass index (BMI),
bleeding and new medications should be assessed
• Congenital hyperlipidemia
• Benign or malignant liver disease at each visit to ensure continued appro-
• Presence or history of stroke or heart priateness of the hormonal contraceptive
attack • Known or suspected breast cancer
product.4
• Known or suspected breast cancer • Acute liver disease
or another estrogen- and progestin- Common side effects should be monitored:
sensitive cancer • Known or suspected pregnancy weight, BMI, depression, skin changes,
• Abnormal undiagnosed vaginal/uterine menstrual symptoms, bleeding irregular-
bleeding
Subcutaneous Depot:
ities, and glucose tolerance for women
DMPA is contraindicated in patients with ac- with prediabetes and diabetes. Women
• Past or present liver tumors or liver
impairment tive thrombophlebitis, history of or current on progestin-only hormonal contraception
thromboembolic disorders, cerebral vascu- should be monitored for ectopic pregnancy
• Hypersensitivity to any components of
the dosage form lar disease, undiagnosed vaginal bleeding, (e.g., lower abdominal pain).4 Women with
breast cancer, significant hepatic disease, an IUD should be monitored for the correct
Relative contraindications: 4,10,62 and pregnancy. 41,42 placement of the device, discharge, infec-
• Presence of migraine headaches tion, fever, or missed periods.47-51
Implant:
• Diabetes mellitus (with complications)
The progestin implant is contraindicated in Women on a CHC should be counseled to
• Gallbladder disease monitor for signs of VTE using the ACHES
patients with breast cancer, progestin-sensi-
• Hypertension (SBP > 140, DBP > 90) tive cancer, hepatic tumors, hepatic disease, acronym. They should report any that occur
pregnancy, history of or current thromboem- to their prescriber or pharmacist:4

12
• Abdominal pain plasma levels of estrogen and proges- Conclusion
• Chest pain or shortness of breath terone, resulting in decreased hormonal Hormonal contraceptive products contain a
contraceptive efficacy.63,64 IUDs, including combination of estrogen and progestin or
• Headaches (new, severe, or associated
with dizziness, fainting, difficulty progestin-releasing IUDs, do not appear to progestin alone and are available in various
speaking, numbness, or weakness in the be affected by CYP3A4 inducers due to their dosage forms. Each patient is unique, and
extremities) direct action on the uterus.22,48-51 many factors may influence the preferred
• Eye problems like blurred vision or loss contraceptive method, including age,
of vision Common CYP3A4 inducers: medical history, desire to return to fertility,
• Severe leg pain, redness, or swelling in • Anti-epileptic drugs that induce CYP adherence issues, and concomitant disease
the calf or thigh 3A4 like phenytoin, carbamazepine,
oxcarbazepine, and topiramate.64 states. Providers should be familliar with the
options available in order to provide women
Drug Interactions • Rifampin63 desiring a hormonal birth control method
CYP3A4 is a major enzyme in the liver that a safe, effective, and patient centered
metabolizes ethinyl estradiol and pro- Epilepsy and combined hormonal
treatment plan.
contraceptive therapy
gesterone in hormonal contraceptives.63
Interactions occur when drugs that induce For women with epilepsy, it is recommend-
the activity of CYP3A4, such as rifampin, ed to opt for an intrauterine system such as
phenytoin, and carbamazepine, increase levonorgestrel IUD or copper IUD to prevent
the metabolism of hormonal contraceptives. interactions with anti-epileptic medica-
The increased metabolism results in lower tions.22

TECHNICIAN CORNER
Pharmacological Treatment Options in Contraceptive Care
• Technicians should be aware of non-pharmacological pregnancy prevention options and where or how to access them, such as physical
location within the retail store or the names of useful mobile device applications.
• Be familiar with proper administration techniques such as how to take, apply, insert, and use various contraceptive methods and triage
any reports or observations of inappropriate technique to the pharmacist.
• Always provide the relevant package insert with each fill of a contraceptive medication so that patients may refer to useful information
about missed dosages, timing, and appropriate administration.
• Ask patients about their adherence to taking or using contraceptives and monitor patients’ refill history to look for consistency and
appropriate timing in refilling any prescribed contraceptive medications.
• Be familiar with common and severe drug reactions or side effects and triage any reports of these to the pharmacist. Being familiar with
these concepts will better enable the pharmacy technician to monitor for polypharmacy.
• Consider asking the patient about any personal or family history of breast cancer, blood clot or DVT history, diabetes, obesity, and
smoking during medication intake or medication reconciliation and triage any findings to the pharmacist.
• During medication intake or medication reconciliation, ask the patient if they are using or receiving any injected or implanted
contraceptives since these may be ordered, administered, or implanted in the physician’s office and, therefore, may not appear on the
patient’s refill history at the pharmacy.

Contributed by: Francesca Morris, MHA, CPhT-Adv

Answers to Active Learning Questions

Question 1: The patch or ring would be a good choice for a woman who has difficulty remembering to take a pill every day, has trouble
swallowing pills, or the patient or provider prefers a product with good cycle control and consistent hormone levels.

Question 2: Progestin-only contraceptives would be a good choice for a woman who has a contraindication to using a product with
estrogen like women over 35 years old who smoke heavily, have a history of VTE, previous stroke, or MI, have uncontrolled high blood
pressure, BMI over 30 kg/m2, or women who are breastfeeding. Progestin-only products like DMPA, implants, and IUDs are also good
choices for long-term contraception.

13
Rx Patient Connection
Common questions healthcare providers may receive from patients with answers that may be provided.

Besides the pills, what other What are some ways I can help to to cause breakthrough bleeding. If you are
contraceptive options are there for remember to take birth control on experiencing nausea, try taking the pill with
me, and are they safe? time? food to see if that helps.
Many hormonal birth control options are Try setting an alarm for the birth control pill
available, including progestin-only pills and be sure to take it once every 24 hours Is it okay to use such as tampons
for patients who cannot tolerate estrogen. around the same time each day. This is if I’m using a vaginal ring for birth
control?
Intrauterine systems and an implant that especially important for the progestin-only
goes in your arm release hormones all year pill, which must be taken every day within It is best to avoid using other vaginal prod-
long and provide long-term contraception. a 3-hour window to prevent pregnancy. If ucts that can interfere with the placement
The contraceptive effects of the pill, the you start taking the pill at 9:00 am, take of the vaginal ring. These include tampons,
ring, and the patch are easily reversed the next dose at 9:00 am or as close to it as they may cause the ring to fall out when
once discontinued. It takes longer to return as possible. For the patch, if you place the removed. If you are using tampons, use
to fertility using other methods, such as patch at 9:00 a.m. on Sunday, be sure to caution when inserting and removing them.
the hormonal shot and IUD system. The replace the patch next week on Sunday at Other vaginal products to avoid when
appropriate method of contraception will 9:00 a.m or within 12 hours to ensure you using the ring are barrier methods such as
ultimately depend on your family planning are protected. Use reminders either on your cervical cap, sponge, female condoms, and
needs, your tolerance to the side effects, phone or on a calendar. Make an X mark on diaphragms as they interfere with the prop-
and your comfort level with how the birth the start day, along with the time to show er ring placement; use male condoms with
control works (intrauterine and intravaginal when you started therapy. You can also spermicides as a backup barrier method
devices might cause more local side effects write yourself a post-it note and place it instead.
and discomfort). The pill offers a simple next to your bed or in your bathroom so you
and convenient route, but they may cause can remember to take your birth control
I smoke regularly. Will that interfere
with my birth control in any way?
more stomach upset, nausea/vomiting, and first thing in the morning. Write down the
problems with adherence due to the strict start and stop times to keep yourself from While smoking is generally not good for the
daily regimen. The non-traditional options, getting confused about when to take the body and can cause problems with lung
such as the ring and patch, are more expen- next dose. function and blood circulation, cigarette
sive and may not be covered by insurance. smoking does not interfere with the efficacy
Be sure to check with your insurance plan I am experiencing bloating and of hormonal contraceptives. However,
to see which contraceptive methods are nausea while I’m on the pill. What smoking does increase the risk of blood
can I do? clots and other cardiovascular complica-
covered and how much your cost will be,
and ask your doctor to provide you with the These are common side effects of an excess tions such as heart attacks and strokes.
safest option available. of estrogen. Your doctor may need to adjust For this reason, you cannot take a com-
the dose of the pill and give you a tablet bined hormonal contraceptive such as the
with a lower pill, ring, or patch if you are 35 and older
dose of estro- and smoke. It is advisable to stop smoking
gen, or they can even if you are under 35 because estrogen
prescribe you creates clotting factors that put you at risk
something that of developing heart attacks and strokes and
does not have increases blood pressure, which can be
estrogen at all, worsened by smoking regularly.
such as a pro-
gestin-only pill. I am overweight, what is the best
However, the birth control option for me?
progestin-only Any product with estrogen is of concern
pill is more likely since combined hormonal contraceptives
are associated with potential weight gain.

14
Estrogen also increases the risk of blood Effectiveness of Nonhormonal Methods of Contraception (Over-the-Counter)
clots, which is higher in overweight, obese,
Perfect Use (% of
or immobile women. The progesterone shot Patients with a Typical Use (% of Patients
(Depo-Provera®) is also known for causing Method Pregnancy) with a Pregnancy)
weight gain. The XulaneTM patch is not indi-
cated in women who weigh 198 lbs or more, Male condom (latex) 2 15
and the TwirlaTM patch is not as effective in Female condom 5 21
women who are overweight (BMI > 25 kg/ Diaphragm 6 12
m2) and is contraindicated in women who FemCap cervical cap 8 14
are obese (BMI > 30 kg/m2). The efficacy of
Spermicides (alone) 18 28
AnnoveraTM and NuvaRing® have also not
been tested in obese women, so we can’t Today sponge 9 12
be sure how effective they are. For this Hormone Free
7 14
reason, one option that is appropriate for Vaginal Gel
a person who is overweight is the proges-
tin-only pill.

Could you go over how to remove the used ring in a waste receptacle out of intercourse for no more than 2 hours, or you
the vaginal ring and dispose of it? reach of pets and children. may not be protected from pregnancy. Be
To remove the NuvaRing® or AnnoveraTM, sure to reinsert the ring after intercourse.
hook the index finger to loop around the Should I remove the vaginal ring If you forget to reinsert or if the ring is out
ring and gently pull down and out. To during sex? for longer than recommended, be sure to
dispose of the NuvaRing®, place the ring The ring typically should not be removed to follow the directions provided by your pre-
in the foil pouch and discard it in a waste avoid interruption in therapy. Either partner scriber or pharmacist to make sure you are
receptacle out of reach of pets and children. may feel the ring during intercourse, but protected from unplanned pregnancy.
To dispose of AnnoveraTM, discard it in the most couples do not report this as problem-
black compact case provided with the drug atic. However, if you are concerned about
product and return it to a drug take-back feeling the ring during intercourse, you may
option if one is available. If no drug-take- remove the NuvaRing® for no more than 3
back program is available, you may place hours. AnnoveraTM may be removed during

Resources for More Information

U.S. Department of Health & Human Services Office The American College of Obstetricians and Gynecol-
on Women’s Health ogists
Birth Control: https://www.womenshealth.gov/a-z-topics/ Birth Control: https://www.acog.org/womens-health/
birth-control-methods healthy-living/birth-control
Emergency Contraception: https://www.womenshealth.
gov/a-z-topics/emergency-contraception Reproductive Health Access Project
Contraception: https://www.reproductiveaccess.org/con-
U.S. Food and Drug Administration traception/
Birth Control: https://www.fda.gov/consumers/free-publi- Resources: https://www.reproductiveaccess.org/resources/
cations-women/birth-control

Planned Parenthood
Birth Control: https://www.plannedparenthood.org/
learn/birth-control

15
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2. Sundaram A, Vaughan B Kost K, et al. Contraceptive failure in the United States: Estimates from the 2006-2010 national survey of family growth. Perspect Sex Reprod Health 2017;49:7-
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3. Thiyagarajan DK, Basit H, Jeanmonod R. Physiology, Menstrual Cycle. StatPearls [internet]. October 30, 2021. Accessed June 24, 2022. http://www.ncbi.nlm.nih.gov/books/NBK500020/
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Basis of Therapeutics, 13e. McGraw Hill; 2017.
11. Teal S, Edelman A. Contraception selection, effectiveness, and adverse effects: a review. JAMA. 2021;326(24):2507-2518.
12. Lawrie TA, Helmerhorst FM, Maitra NK, Kulier R, Bloemenkamp K, Gülmezoglu AM. Types of progestogens in combined oral contraception: effectiveness and side-effects. Cochrane Da-
tabase Syst Rev. 2011;(5):CD004861. doi:10.1002/14651858.CD004861.pub2
13. FDA drug safety communication: updated information about the risk of blood clots in women taking birth control pills containing drospirenone. U.S. Food &Drug Administration (FDA).
February 13, 2018. Accessed July 16, 2022. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-updated-information-about-risk-blood-clots-wom-
en-taking-birth-control
14. What birth control brands: How to choose what’s right for you. Healthline. December 7, 2021. Accessed July 10, 2022. https://www.healthline.com/health/birth-control/birth-control-pill-
brands
15. Edelman A, Micks E, Gallo MF, Jensen JT, Grimes DA. Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database of System-
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16. Li J, Panucci G, Moeny D, et al. Association of Risk for Venous Thromboembolism With Use of Low-Dose Extended- and Continuous-Cycle Combined Oral Contraceptives: A Safety Study
Using the Sentinel Distributed Database. JAMA Internal Medicine. 2018;178(11):1482-1488. doi:10.1001/jamainternmed.2018.4251
17. Stacey D. An Overview of Continuous Birth Control Pills. Verywell Health. February 21, 2021. Accessed April 24, 2022. https://www.verywellhealth.com/continuous-birth-control-906728
18. Meet | Lo Loestrin® Fe. Accessed April 24, 2022. https://www.loloestrin.com/meet-lo-loestrin
19. Amethyst, the Generic Lybrel, Means No More Periods. Verywell Health. Accessed April 26, 2022. https://www.verywellhealth.com/amethyst-the-continuous-birth-control-pill-906729
20. Fischer JAJ, Sasai CS, Karakochuk CD. Iron-containing oral contraceptives and their effect on hemoglobin and biomarkers of rron status: a narrative review. Nutrients 2021;13:2340.
21. Galzote RM, Rafie S, Teal R, Mody SK. Transdermal delivery of combined hormonal contraception: a review of the current literature. Int J Womens Health. 2017;9:315-321. doi:10.2147/
IJWH.S102306
22. Schwenkhagen AM, Stodieck SRG. Which contraception for women with epilepsy? Seizure - European Journal of Epilepsy. 2008;17(2):145-150. doi:10.1016/j.seizure.2007.11.013
23. Grossman Barr N. Managing adverse effects of hormonal contraceptives. Am Fam Physician. 2010;82(12):1499-1506.
24. de Melo NR. Estrogen-Free Oral Hormonal Contraception: Benefits of the Progestin-Only Pill. Womens Health. 2010;6(5):721-735. doi:10.2217/WHE.10.36
25. Milanes-Skopp R, Nelson AL. Transdermal contraceptive patches: current status and future potential. Expert Review of Clinical Pharmacology. 2009;2(6):601-607. doi:10.1586/ecp.09.37
26. Xulane. Prescribing information. Mylan Pharmaceuticals; 2022. Accessed May 9, 2022. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?type=display&setid=f7848550-086a-
43d8-8ae5-047f4b9e4382
27. Twirla. Prescribing information. Corium International, Inc.; 2022. Accessed May 9, 2022. https://www.twirla.com/pdf/Twirla%20FINAL%20USPI%20PPI%20IFU.pdf
28. Brache V, Faundes A. Contraceptive vaginal rings: a review. Contraception. 2010;82(5):418-427. doi:10.1016/j.contraception.2010.04.012
29. NuvaRing. Prescribing information. Merck & Co., Inc.; 2020. Accessed June 20, 2022. https://www.nuvaring.com/static/pdf/nuvaring-pi.pdf
30. Annovera. Prescribing information. TherapeuticsMD, Inc.; 2022. Accessed May 7, 2022.
https://www.annovera.com/pi.pdf
31. Barriga Pooley P, Von Hoveling A, Galán G, López Berroa J. Analysis and new contraception frontiers with combined vaginal rings. Gynecol Endocrinol. 2020;36(6):475-478. doi:10.1080/0
9513590.2020.1729730
32. Temmerman M. A new woman-controlled contraceptive vaginal ring: a global step forward. The Lancet Global Health. 2019;7(8):e986-e987. doi:10.1016/S2214-109X(19)30289-X
33. Contraception: Practice Essentials, Overview, Periodic Abstinence. Published online January 25, 2022. Accessed May 6, 2022. https://emedicine.medscape.com/article/258507-over-
view#a5
34. Rivlin K, Isley MM. Patient-centered Contraceptive Counseling and Prescribing. Clinical Obstetrics & Gynecology. 2018;61(1):27-39. doi:10.1097/GRF.0000000000000337
35. Summary chart of U.S. medical eligibility criteria for contraceptive use. Centers for Disease Control and Prevention. 2020. Accessed July 10, 2022. https://www.cdc.gov/reproductive-
health/contraception/pdf/summary-chart-us-medical-eligibility-criteria_508tagged.pdf
36. Slynd. Prescribing information. Exeltis USA, Inc.; 2019. Accessed July 27, 2022. http://slynd.com/wp-content/uploads/2019/08/prescribing-information.pdf
37. Baker CC, Chen MJ. New Contraception Update — Annovera, Phexxi, Slynd, and Twirla. Curr Obstet Gynecol Rep. 2022;11(1):21-27. doi:10.1007/s13669-021-00321-4
38. Ortho Micronor. Prescribing information. Ortho-McNeil; 2008. Accessed July 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/016954s101lbl.pdf
39. Norethindrone. Mayo Clinic. July 1, 2022. Accessed July 16, 2022. https://www.mayoclinic.org/drugs-supplements/norethindrone-oral-route/description/drg-20137986
40. Drospirenone. Mayo Clinic. June 1, 2022. Accessed July 16, 2022. https://www.mayoclinic.org/drugs-supplements/drospirenone-oral-route/description/drg-20465072
41. Medroxyprogesterone. Lexi Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
42. DEPO-PROVERA- Medroxyprogesterone Acetate Injection, Suspension. Highlights of Prescribing Information. Pharmacia & Upjohn Company LLC; 2020. Accessed May 12, 2022. https://
rsc.niaid.nih.gov/sites/default/files/medroxypogesterone-acetate_depo-provera-ci_jan-2017.pdf
43. DEPO-SUBQ PROVERA – medroxyprogesterone acetate injection, suspension. Prescribing information. Pharmacia & Upjohn Company LLC.;2020. Accessed May 12, 2022. https://label-
ing.pfizer.com/showlabeling.aspx?id=549
44. Update to U.S. Selected Practice Recommendations for Contraceptive Use: Self-Administration of Subcutaneous Depot Medroxyprogesterone Acetate. Centers for Disease Control and
Prevention. May 21, 2021. Accessed May 12, 2022. https://www.cdc.gov/mmwr/volumes/70/wr/mm7020a2.htm
45. Nexplanon. Prescribing Information. Organon Global Inc.;2021. Accessed May 12, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021529s018lbl.pdf
46. Etonogestrel. Lexi Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
47. Paragard. Prescribing Information. Cooper Surgical;2020. Accessed May 13, 2022. https://www.paragard.com/wp-content/uploads/2018/10/PARAGARD-PI.pdf
48. Liletta. Prescribing Information. Actavis Pharma, Inc.;2015. Accessed May 13, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/206229s000lbl.pdf
49. Skyla. Prescribing Information. Bayer HealthCare Pharmaceuticals Inc.; 2017.Accessed May 13, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/203159s007lbl.pdf
50. Kyleena. Prescribing Information. Bayer Healthcare Pharmaceuticals Inc.; 2016. Accessed May 13, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208224s000l-
bl.pdf
51. Mirena Prescribing Information. Bayer Healthcare Pharmaceuticals Inc.; 2021.Accessed May 13, 2022. https://labeling.bayerhealthcare.com/html/products/pi/Mirena_PI.pdf
52. Yland J, Bresnick K, Hatch E, et al. Pregravid contraceptive use and fecundability: prospective cohort study. BMJ. 2020;371:m3966
53. Levonorgestrel. Lexi Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
54. Copper IUD. Lexi Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL.
55. Reed SD, Zhou X, Ichikawa L, et al. Intrauterine device-related uterine perforation incidence and risk (APEX-IUD): a large multisite cohort study. Lancet. 2022 Jun 4;399(10341):2103-
2112. doi: 10.1016/S0140-6736(22)00015-0. PMID: 35658995.
56. Berenson AB, Odom SD, Breitkopf CR, Rahman M. Physiologic and psychologic symptoms associated with use of injectable contraception and 20 microg oral contraceptive pills. Am
J Obstet Gynecol. 2008;199(4):351.e1-351.e12.
57. Loder EW, Buse DC, Golub JR. Headache as a side effect of combination estrogen-progestin oral contraceptives: a systematic review. Am J Obstet Gynecol. 2005;193(3 pt 1):636-649.
58. Combined Hormonal Contraception. Faculty of Sexual and Reproductive Healthcare. November 2020. Accessed July 15, 2022. https://www.fsrh.org/standards-and-guidance/docu-
ments/combined-hormonal-contraception/
Test Questions Pharmacy Technician
To receive CE, access the issue and take the test online at rxconsultant.com

1. AnnoveraTM is available in which of the following dosage forms? 8. Which of the following is true regarding ErrinTM?
a. Oral pill a. Breakthrough bleeding is common when starting therapy
b. Patch b. Nausea and breast tenderness are common side effects associated
c. Ring with this therapy
c. Withdrawal bleeding occurs during week 4 of the cycle due to
d. Injection hormone-free interval
d. You should avoid smoking since smoking is contraindicated with this
2. Which of the following hormonal birth control options is an injection birth control
administered by a healthcare provider?
a. Depo-Provera® 9. Which of the following is a sign of venous thromboembolism (VTE)?
b. JencyclaTM a. Severe pain and swelling in the calf
c. AnnoveraTM b. Hypotension
d. Mircette® c. Wheezing
d. Jaundice
3. SlyndTM contains which of the following active ingredients?
a. Norethindrone 10. Which of the following is true about IUDs?
b. Drospirenone a. Antibiotics should be given before inserting an IUD
c. Medroxyprogesterone b. There are no known drug interactions with the copper IUD
d. Ethinyl estradiol/levonorgestel c. IUDs are contraindicated immediately postpartum
d. All IUDs can remain in place for 10 years
4. AmethystTM is available in which of the following dosage forms?
a. Oral pill 11. Which of the following is a contraindication to the use of combined
b. Patch hormonal contraception?
c. Ring a. History of heart attack
d. Injection b. Diabetes type 2
c. Hepatitis C
5. Which of the following hormonal birth control options is a transdermal d. Age over 35 years
patch applied weekly by the patient?
a. XulaneTM 12. Which of the following is a common side effect in patients using
b. Kyleena® combined hormonal contraceptives?
c. MonoNessa® a. High Blood pressure
d. Quasense TM
b. Osteoporosis
c. Liver failure
6. LevonestTM is which of the following types of hormonal contraception? d. Hypothyroidism
a. Quadraphasic POP
b. Monophasic COC
c. Triphasic COC
d. Biphasic POP

7. AM is a 36-year-old woman taking carbamazepine for epilepsy. She

was recently prescribed KarivaTM for birth control and is now in week
two of therapy. Which of the following is a concern for AM?
a. Carbamazepine induces CYP3A4 and can increase the exposure to
estrogen found in KarivaTM
b. Carbamazepine can decrease the effectiveness of KarivaTM and
increase the chance of ovulation and pregnancy
c. Carbamazepine inhibits CYP3A4 and increases the risk of
breakthrough bleeding
d. Carbamazepine can lead to loss of fertility if taken with KarivaTM
For mail-in submissions:

First Name:
Last Name:
Test Questions Pharmacist & Nurse
To receive CE, access the issue and take the test online at rxconsultant.com

1. Which hormone is responsible for ensuring the uterine lining is growing 7. MJ is a 35-year-old woman who has trouble remembering to take
and thickening for the chance of possible pregnancy? birth control daily. She wants something that will not expose her to
a. LH too much estrogen and will give her better control of start and stop
b. FSH times. She also wants something that will not need to be picked up at
the pharmacy every month. Which of the following would be the best
c. Estrogen option for her?
d. Progesterone a. Ortho Tri-Cyclen®
b. Camila®
2. Which of the following is an appropriate counseling point to provide for
ErrinTM? c. XulaneTM
a. Breakthrough bleeding is common when starting therapy d. AnnoveraTM
b. Nausea and breast tenderness are common side effects associated
with this therapy 8. Which of the following monitoring parameters is recommended for
patients using hormonal contraceptives?
c. You can expect withdrawal bleeding in week 4 of the cycle due to
hormone-free interval a. Blood pressure
d. You should avoid smoking while on the pill since smoking is b. Bone mineral density
contraindicated with this birth control c. Liver function
d. Thyroid function
3. AM is a 36-year-old woman taking carbamazepine for epilepsy. She
was recently prescribed KarivaTM for birth control, and is now in week
two of therapy. Which of the following is a concern for AM? 9. Which of the following is true about IUDs?
a. Carbamazepine induces CYP3A4 and can increase the exposure to a. Antibiotics should be given before inserting an IUD
estrogen found in KarivaTM b. There are no known drug interactions with the copper IUD
b. Carbamazepine can decrease the effectiveness of KarivaTM and c. IUDs are contraindicated immediately postpartum
increase the chance of ovulation and pregnancy d. All IUDs can remain in place for 10 years
c. Carbamazepine inhibits CYP3A4 and increases the risk of
breakthrough bleeding
10. Progestin-only pills are preferred in a woman with which of the
d. Carbamazepine can lead to loss of fertility if taken with KarivaTM following health factors?
a. Hyperthyroidism
4. SC is a 25-year-old woman with a BMI of 29 kg/m2. She has a history
b. Smoker over 35 years of age
of diabetes type 2 and is 4 weeks postpartum and breastfeeding. She
would like to start a hormonal contraceptive to avoid pregnancy. Which c. BMI of 28 kg/m2
method will be the safest option for her, given her health status? d. Gallbladder disease
a. Ortho Tri-Cyclen®
b. Camila® 11. Menstrual bleeding occurs when which of the following hormone levels
begins to drop during the menstrual cycle?
c. XulaneTM
a. Estrogen
d. NuvaRing®
b. FSH
5. Which of the following is an appropriate counseling point for the c. Progesterone
TwirlaTM patch? d. LH
a. Apply one patch and wear for weeks 1 – 3, then remove during
week 4 12. Which of the following side effects of a combined hormonal
b. The patch is less effective than combined hormonal contraceptive contraceptive may be managed by increasing the progestin dose?
pills a. Late cycle spotting
c. If the patch is off for longer than 24 hours a backup method of b. Vaginal dryness
contraception must be used for seven days
c. Breast tenderness
d. TwirlaTM may improve symptoms of migraine with aura
d. Hirsutism
6. Which of the following contraceptive methods is the most effective in
preventing pregnancy?
a. DMPA
b. Vaginal ring For mail-in submissions:
c. Transdermal patch
d. Progestin only pill First Name:
Last Name:
EDITORS
Cara M. Brock, PharmD Cherie Dillon, PharmD Jim Chan, PharmD, PhD Nina Escasa, PharmD
Managing Editor, Associate Editor, Associate Editor, Associate Editor,
The Rx Consultant The Rx Consultant The Rx Consultant The Rx Consultant

PHARMACIST LEARNING OBJECTIVES

1. Identify the hormones involved in regulating the menstrual cycle
2. List the mechanism of action, dosage forms, contraindications, dosing, adverse effects, drug-drug and drug-supplement interactions, and
monitoring of hormonal contraceptive products
3. Recognize the effectiveness of hormonal contraceptive treatment options

TECHNICIAN LEARNING OBJECTIVES

1. Recall hormonal contraceptive treatment options, including dosage forms, route of administration, and brand/generic names.
2. Identify the drug-drug and drug-supplement interactions of hormonal contraceptives.
3. Recognize common and severe side effects and contraindications associated with hormonal contraceptives

ACCREDITATION
PharmCon, Inc. is accredited by the Accreditation Council for Nursing (Provider Number CEP 13649) and the Florida Board of
Pharmacy Education as a provider of continuing pharmacy Nursing (Provider Number 50-3515). Activities approved by the CA
education. BRN and the FL BN are accepted by most State Boards of Nursing.
PharmCon, Inc. reports CPE credits to CPE Monitor automatically ACPE accredited programs provided by PharmCon, Inc. meet
after credit is earned. Your NABP ePID and birth date must be in requirements for American Nurses Credentialing Center (ANCC)
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PharmCon, Inc. is approved by the California Board of Registered

TARGET AUDIENCE AUTHOR DISCLOSURE

Pharmacists, Pharmacy Technicians, Advanced Practice Drs. Nawaz and Schneider, authors of this educational activity, have no
Registered Nurses, Registered Nurses relevant financial relationship(s) with ineligible companies to disclose.

ACPE UNIVERSAL ACTIVITY NUMBER

PHARMACIST: 0798-0000-22-149-H01-P Activity Type: Knowledge-Based

PHARMACY TECHNICIAN: 0798-0000-22-149-H01-T Release Date: 08/25/2022

CE Broker Number: 20-915241 Expiration Date: 08/25/2025

All opinions expressed by the author(s) are strictly their own and not necessarily None of the contents of this publication may be reproduced in any form without the written
approved or endorsed by PharmCon. permission of the publisher.
Consult full prescribing information on any drugs or devices discussed. Credit for this program is issued by passing the final test hosted at www.RxConsultant.com
PharmCon freeCE & PharmCon Rx Consultant are divisions of KnowFully Learning Group. with a score of 70% or higher.
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