Sem 16 Lectura 1 Anticoncepcion

2/11/2017 Overview of the use of estrogen-progestin contraceptives - UpToDate
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Overview of the use of estrogen-progestin contraceptives
Authors: Kathryn A Martin, MD, Robert L Barbieri, MD

Section Editor: William F Crowley, Jr, MD
Deputy Editor: Kathryn A Martin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Oct 2017. | This topic last updated: Aug 17, 2016.
INTRODUCTION Oral contraceptives (OCs) are a reliable form of contraception and have
noncontraceptive benefits, as well. Furthermore, the decrease in both estrogen and progestin content in the
last decade has led to a reduction in both side effects and cardiovascular complications [1]. As a result, these
preparations are a safe contraceptive option for many women. While the US Food and Drug Administration
(FDA) had previously set upper age limits for OC use as 35 years for smokers and 40 years for nonsmokers,
all references to age limits were removed in 1989 for healthy, nonsmoking women. Thus, OCs can be given
until menopause in such women.
This topic will review the general principles of the use of combined estrogen-progestin OCs, including
pharmacology, mechanisms of action, indications, contraindications, efficacy, and the different preparations
that are available. Progestin-only OCs, the side effects that may be associated with OCs, other forms of
estrogen-progestin contraception, and the topic of contraception in general are discussed separately. (See
"Progestin-only pills (POPs) for contraception" and "Risks and side effects associated with estrogen-progestin
contraceptives" and "Transdermal contraceptive patch" and "Contraceptive counseling and selection".)
PHARMACOLOGY The discovery in 1938 that addition of an ethinyl group to estradiol resulted in both an
orally active estrogen compound and a dramatic increase in estrogenic potency was a major advance in
steroid biochemistry. This compound, known as ethinyl estradiol, is the estrogen in nearly all oral
contraceptives (OCs) currently used.
Soon thereafter, ethinyl substitution of testosterone also was found to result in an orally active compound
(ethisterone). Removal of the carbon at the C-19 position of ethisterone changed it from an androgen to a
progestin. This finding resulted in the development of a class of progestins referred to as 19-nortestosterone
derivatives. Included in this class are commonly used progestins such as norethindrone, norethindrone
acetate, and levonorgestrel. Ethynodiol diacetate, another progestin in this category, also has significant
estrogenic activity (table 1).
All of these testosterone-derived progestins bind to the androgen receptor and have some residual
androgenic activity. The adverse metabolic effects of OCs, such as the reduction in serum high-density
lipoprotein (HDL) cholesterol concentrations, are the result of the androgenic activity of the progestin. New
progestins have been developed with less androgenic activity (table 1). (See 'Progestin component' below.)
MECHANISMS OF ACTION
Contraception Oral contraceptives (OCs) have several mechanisms of action, including suppression of
hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin secretion. The most
important mechanism for providing contraception is inhibition of the midcycle luteinizing hormone (LH) surge,
so that ovulation does not occur (see "Physiology of the normal menstrual cycle"). Combination OCs are
potent in this regard, but progestin-only pills are not.
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Another mechanism of contraceptive action is suppression of ovarian folliculogenesis (via suppression of

pituitary follicle-stimulating hormone [FSH] secretion). However, a substantial number of women develop
follicles while taking an OC that contains lower doses of ethinyl estradiol (20 to 35 mcg) [2,3].
Clinicians often recommend that back-up contraception be used in the first cycle of OC use, due to concern
that early follicular development could result in breakthrough ovulation (most package inserts recommend
starting the pill on the first Sunday after menses, which could be as late as day 7). In a study of 140 women
randomly assigned to start their OC (containing 30 mcg ethinyl estradiol/day) on day 1, 4, or 7 of menses,
follicular development (diameter >13 mm) was more common with the later start days (10.3, 17.2, and 44.4
percent for days 1, 4, and 7, respectively) [4]. However, rates of ovulation were no different in the three
groups (7, 3, and 0 percent, respectively). Thus, back-up contraception might not be necessary in the first
month of OC use, but a larger study is needed before changing clinical practice.
Progestin-related mechanisms also contribute to the contraceptive effect (see "Progestin-only pills (POPs) for
contraception", section on 'Mechanism of action'). These include:
Effects on the endometrium, rendering it less suitable for implantation. The daily progestin exposure
leads to endometrial decidualization and eventual atrophy (eg, with continuous or extended-cycle OC
regimens). (See 'Continuous pill' below.)
Alterations in cervical mucus, which becomes less permeable to penetration by sperm.
Impairment of normal tubal motility and peristalsis.
Use in hyperandrogenism Combination OCs are useful for the treatment of women with
hyperandrogenism (most often due to polycystic ovary syndrome). While preparations containing less
androgenic progestins are thought to be the best option in this population, clinical trial data have not
demonstrated that they are more effective than OCs containing a more androgenic progestin such as
levonorgestrel (table 2). (See "Treatment of hirsutism", section on 'Oral contraceptives' and "Hormonal
therapy for women with acne vulgaris", section on 'Oral contraceptives'.)
Among the beneficial effects of an OC in women with hyperandrogenism are:
Inhibition of gonadotropin secretion and thereby a decrease in ovarian androgen secretion

An increase in serum sex hormone-binding globulin (SHBG) concentrations, which results in increased
binding of androgens and a decrease in serum free androgen concentrations
Inhibition of adrenal androgen secretion [5]; the mechanism of the last effect is not well understood
Use in other disorders There are many other indications for the use of OCs other than contraception and
hyperandrogenism. These include the treatment of dysmenorrhea, menorrhagia, other menstrual cycle
disorders such as hypothalamic amenorrhea, and as hormone replacement in women with primary
hypogonadism. OCs have also been used for the treatment of premenstrual dysphoric disorder (PMDD).
(See "Treatment of premenstrual syndrome and premenstrual dysphoric disorder".)
EFFICACY When taken properly, oral contraceptives (OCs) are a very effective form of contraception.
Although the perfect-use failure rate is 0.1 percent, the typical-use failure rate is 8 percent, due primarily to
missed pills or failure to resume therapy after the seven-day pill-free interval (table 3). OCs are available in
many formulations (table 4), and there is no evidence that generic OCs are less effective than brand name
OCs or that different OCs have different perfect-use failure rates, although few comparative studies have
been performed [6-8].
Effect of missed pills Missed pills (particularly if the seven-day hormone-free interval is extended on
either end) are a common cause of contraceptive failure.
If a single pill is missed anywhere in the packet, the forgotten pill needs to be taken when noticed and the
next pill is taken when it is due, which may mean taking two pills on the same day. No additional
contraception is required.
Back-up contraception is generally needed if two or more consecutive hormonal pills are missed [9-12].
Women should take one of the missed active (hormonal) pills as soon as possible and then continue
taking one pill each day as prescribed. Depending on when she remembers her missed pill, she may
take two pills on the same day. If pills were missed in the last week of hormone pills, days 15 to 21 of a
28-day pack, omit the hormone-free week by finishing the hormone pills in current pack and start a new
pack the next day. If unable to start a new pack, use back-up until hormonal pills from a new pack are
taken for seven consecutive days.
If the two or more pills are missed in the first week of the cycle and unprotected intercourse occurs
during this week, use of emergency contraception could decrease the risk of pregnancy.
This approach is similar to that suggested by the 2013 US Selected Practice Recommendations for
Contraceptive Use (table 5) [9].
Extra pills If the patient takes two pills in one day by mistake, she should resume her normal schedule of
taking one pill daily the next day; she should not skip a day. She will complete the pill pack one day early.
Effect of weight While some epidemiologic studies suggest that being overweight or obese may increase
the risk of becoming pregnant while on OCs [13,14], another reported that the association was attenuated
after adjustment for age, race/ethnicity, and parity [15]. Clinical trial data are somewhat limited [16].
In a low-dose (25 mcg) OC trial that enrolled 876 overweight (body mass index [BMI] 25 kg/m2) and 1934
normal women (BMI <25 kg/m2), those in the overweight group had a higher risk of becoming pregnant
(relative risk [RR] 1.39) [17]. One possible explanation for the higher failure rate among overweight women
would be incomplete suppression of the hypothalamic-pituitary-ovarian axis, resulting in follicular
development and ovulation. However, in a separate trial of 96 normal and 54 obese women (BMI <25 or 30
kg/m2, respectively), rates of follicular development and ovulation (as assessed by pelvic ultrasound) were
similar in both groups [18]. Inconsistent or nonuse of the pill, but not obesity, was associated with ovulation.
Thus, for overweight or obese women who take OCs, adherence may be particularly important. (See
"Contraception counseling for obese women".)
Return of menses after stopping For many women, menses returns within 30 days after stopping the
pill. But menses and fertility should return to normal in almost all women by 90 days. This is true for standard
28-day regimens, as well as the extended and continuous regimens. Therefore, women who do not
menstruate three months after stopping the pill should undergo the same evaluation for amenorrhea as any
woman with amenorrhea. (See "Risks and side effects associated with estrogen-progestin contraceptives",
section on 'Post-pill amenorrhea' and "Risks and side effects associated with estrogen-progestin
contraceptives".)
ADMINISTRATION
Issues to consider when beginning hormonal contraception The 2013 US Selected Practice
Recommendations for Contraceptive Use provide an overview of factors to consider when initiating
contraception in healthy women, such as how to help a woman initiate use of a contraceptive method, which
examinations and tests are needed before initiating use (table 5), what regular follow-up is needed, and how
to address problems that often arise during use [9].
Screening requirements Hormonal contraception can be safely provided after a careful medical history
and blood pressure measurement. While breast exams, pap smears, and screening for sexually transmitted
diseases are important, most groups, including the American College of Obstetricians and Gynecologists
(ACOG), the World Health Organization (WHO), and the Royal College of Obstetricians and Gynecologists
(RCOG), agree that these procedures are not necessary before a first prescription for oral contraceptives
(OCs) [19]. Documentation of body mass index (BMI) prior to starting OCs is suggested because obese
women are at greater risk for venous thromboembolism with OC use.
Initiation OCs can be started anytime during the cycle (algorithm 1). We prefer the quick start method in
which the woman begins taking OCs on the day that she is given the prescription, as long as pregnancy is
reasonably excluded (table 6) [20]. An alternative is the Sunday start approach where the woman starts the
pill on the first Sunday after her period begins (because most pill packs are arranged for a Sunday start to
avoid withdrawal bleeding on a weekend). Some form of back-up contraception is needed for the first seven
days of use if one chooses the quick or Sunday start methods because the full contraceptive effect might not
be provided immediately.
The US Selected Practice Recommendations for Contraceptive Use suggests that if the pill is started >5 days
after the onset of menses, back-up contraception should be used for the first seven days [9].
The first day start requires that the woman begin the pill on the first day of menses, which provides the
maximum contraceptive effect in the first cycle; back-up contraception for the first seven days of use is not
needed. The disadvantages of the Sunday and first day start approaches are that some women do not get
around to filling their prescriptions or become confused about instructions or become pregnant before it is
time to start the OC.
OCs are given on a monthly or an extended cycle. An extended-cycle regimen reduces the number of
episodes of withdrawal bleeding per year and can completely eliminate these episodes. The hormone-free
interval may be zero, two, four, or seven days. Shortening the hormone-free interval may reduce symptoms
associated with hormone withdrawal (eg, headache, pelvic pain). (See 'Continuous pill' below and "Hormonal
contraception for suppression of menstruation".)
Hormonal contraception can be continued until the age of menopause (age 51 to 55 years) in healthy
nonsmoking women [21].
Follow-up Contraceptive follow-up can be addressed during routine periodic exams scheduled for
other health maintenance issues. A specific follow-up exam just to address contraception is not needed.
Women should be encouraged to return if they have any concerns about their method or want to discontinue
or switch methods. Continuation of the contraceptive method is enhanced if the patient receives a
prescription, or even better, a supply for a full year of pills [20,22].
Contraindications There are a number of absolute and relative contraindications to the use of OCs, as
well as medical conditions that may affect contraceptive choice; all are summarized in the WHO and Centers
for Disease Control (CDC) tables that are described in the following sections.
World Health Organization The WHO has published comprehensive tables of medical conditions and
personal characteristics that may affect contraceptive choice (hormonal contraception and intrauterine
devices [IUDs]).
These tables can be found online (WHO Medical Eligibility Criteria for Contraceptive Use 2015).
Centers for Disease Control The CDC modified the WHO tables for medical eligibility criteria for
contraceptive use [23]. Selected WHO recommendations were adapted for United States clinicians and
patients, the number of medical conditions was expanded and recommendations added, and contraceptive
methods not available in the United States were removed. These tables were updated in 2016 and are
available on the CDC website (Medical Eligibility Criteria, CDC).
Based upon the CDC tables, some of the medical conditions that represent an unacceptable health risk if a
combined estrogen-progestin OC was initiated include (see "Risks and side effects associated with estrogen-
progestin contraceptives"):
Age 35 years and smoking 15 cigarettes per day
Multiple risk factors for arterial cardiovascular disease (such as older age, smoking, diabetes, and
hypertension)
Hypertension (systolic 160 mmHg or diastolic 100 mmHg)
Venous thromboembolism
Known thrombogenic mutations
Known ischemic heart disease
History of stroke
Complicated valvular heart disease (pulmonary hypertension, risk for atrial fibrillation, history of subacute
bacterial endocarditis)
Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies)
Migraine with aura at any age
Breast cancer
Cirrhosis
Hepatocellular adenoma or malignant hepatoma
Risks and side effects Risks and side effects of OCs are influenced by the type, dose, and route of
administration of estrogen, as well as the dose and type of the progestin. Lower estrogen dose OCs are
associated with reduced risks of venous thromboembolism [24,25] and bothersome estrogenic side effects,
such as breast tenderness, nausea, and bloating [26], compared with higher estrogen dose OCs. Very-low-
dose estrogen OCs (10 to 20 mcg) are associated with higher rates of bleeding pattern disruptions, which is a
common reason for discontinuation of this method [27]. Regardless of the formulation used, the number of
bleeding/spotting days is highest in the first three months of use and decreases thereafter [28]. (See
"Management of unscheduled bleeding in women using contraception", section on 'Estrogen-progestin
contraceptives'.)
The risks and side effects of estrogen-progestin OCs are discussed in detail separately. (See "Risks and side
effects associated with estrogen-progestin contraceptives".)
NONCONTRACEPTIVE BENEFITS In addition to high contraceptive efficacy, estrogen-progestin

contraceptives are used as treatment for acne, hirsutism, menorrhagia, dysmenorrhea, pelvic pain, and
premenstrual syndrome (PMS). Estrogen-progestin contraceptives also reduce the risk of ovarian and
endometrial cancer [29].
Menstrual cycle disorders
Menorrhagia (see "Hormonal contraception for suppression of menstruation")
Dysmenorrhea (see "Treatment of primary dysmenorrhea in adult women", section on 'Hormonal

contraception')
PMS and premenstrual dysphoric disorder (PMDD) (continuous pills or pills with shortened pill-free
interval); however, the pill is not considered a first-line therapy for PMS/PMDD (see "Treatment of
premenstrual syndrome and premenstrual dysphoric disorder")
Prevention of menstrual migraine (continuous pill) (see "Estrogen-associated migraine", section on

'Preventive therapies')
Hyperandrogenism
Acne (see "Hormonal therapy for women with acne vulgaris")
Hirsutism (see "Treatment of hirsutism")
Gynecologic disorders
Bleeding due to leiomyomas (see "Overview of treatment of uterine leiomyomas (fibroids)", section on
'Estrogen-progestin contraceptives')
Pelvic pain due to endometriosis (see "Endometriosis: Treatment of pelvic pain", section on 'Estrogen-
progestin contraceptives')
Cancer risk reduction
Decreased risk of endometrial cancer and ovarian cancer; data are conflicting on whether there is a
similar reduction in risk in BRCA1 or BRCA2 ovarian cancers (see "Endometrial carcinoma:
Epidemiology and risk factors", section on 'Hormonal contraceptives' and "Epithelial carcinoma of the
ovary, fallopian tube, and peritoneum: Histopathology") [30,31]
Decreased risk of colon cancer
Ovarian cysts Although hormonal contraceptives are often prescribed to suppress large functional
ovarian cysts, a systematic review of available data concluded that functional cysts do not regress more
quickly with estrogen-progestin contraceptive therapy when compared with expectant management [29,32].
USE DURING LACTATION The World Health Organization (WHO) and the American College of
Obstetricians and Gynecologists (ACOG) have made recommendations for nonhormonal and hormonal
contraception during lactation. This topic is reviewed in detail elsewhere. (See "Postpartum contraception:
Initiation and methods", section on 'Impact on lactation'.)
DRUG INTERACTIONS The metabolism of oral contraceptives (OCs) is accelerated by any drug that
increases liver microsomal enzyme activity such as phenobarbital, phenytoin, griseofulvin, and rifampin. As a
result, the contraceptive efficacy of an OC is likely to be decreased in women taking these drugs [33,34].
Anticonvulsants We agree with the World Health Organization (WHO) and suggest that women taking
anticonvulsants including phenytoin, carbamazepine, barbiturates, primidone, topiramate, or
oxcarbazepine should not use hormonal contraception (with the exception of depo-medroxyprogesterone
acetate) [35]. They add, however, that hormonal contraception is reasonable if the patient understands
the risks and cannot use other methods. (See "Overview of the management of epilepsy in adults",
section on 'Contraception'.)
Anticonvulsants that do not appear to reduce contraceptive efficacy include gabapentin, levetiracetam,
and tiagabine [36]. In contrast, estrogen-progestin OCs increase lamotrigine clearance [37], resulting in a
decrease in plasma lamotrigine concentrations by 45 to 60 percent. This interaction raises concerns
about adequate seizure control if an OC and lamotrigine are used in combination [37-39]. (See
"Overview of the management of epilepsy in adults", section on 'Contraception'.)
Antibiotics Rifampin is the only antibiotic proven to decrease serum ethinyl estradiol and progestin
levels in women taking OCs [33]; a nonhormonal contraceptive method is recommended in these women
[21]. Rifampin may also decrease the effectiveness of the transdermal (Xulane) and vaginal ring
(NuvaRing) preparations; an alternate form of contraception should be used in this situation, as well.
In spite of anecdotal reports of OC failure, other antibiotics have not been proven to affect the
pharmacokinetics of ethinyl estradiol [40-43]. For women taking antibiotics other than rifampin with OCs,
back-up contraception is not required. Griseofulvin, an antifungal agent, has been associated with
contraceptive failure in several case reports [44]. However, data are limited and the WHO concludes that
hormonal contraception is reasonable for women on griseofulvin [35].
Vaginal miconazole suppositories and creams do not appear to affect serum steroid levels in women
using the contraceptive vaginal ring [45].
Other St. John's wort induces cytochrome P450, which may increase OC metabolism and reduce
therapeutic efficacy [46]. Two small clinical trials of women on OCs reported an increase in breakthrough
bleeding (BTB) with the addition of St. John's wort [47,48]. Although serum progesterone concentrations
were unchanged, concerns remain that contraceptive efficacy could be reduced with this combination.
The opposite effect, a decrease in metabolism of the administered estrogen, can occur with fluconazole
[49] and possibly grapefruit juice [50,51], resulting in a higher than expected serum concentration of
ethinyl estradiol. Whether this results in untoward effects is unclear.
Limited data suggest that grapefruit juice may inhibit metabolism of exogenous ethinyl estradiol and 17-
beta estradiol, resulting in higher serum concentrations.
Drug interactions between OCs and many of the drugs used to treat human immunodeficiency virus (HIV)
infection are discussed elsewhere. (See "HIV and women", section on 'Choice of contraception'.)
AVAILABLE PREPARATIONS There are two types of oral contraceptive (OC) pills: combination pills that
contain both estrogen and progestin, and the progestin-only pill (also referred to as the "mini-pill") (table 4).
Combination pills are packaged in 21-day or 28-day cycles. The last seven pills of a 28-day pack are placebo
pills, which are thought by some to improve patient compliance, although this has never been proven.
Oral estrogen-progestin contraceptives are available over-the-counter in the majority of countries worldwide,
but by prescription only in 30 percent of countries, including the United States [52].
A chewable formulation (Femcon Fe) is available with 21 tablets containing ethinyl estradiol (35 mcg) and
norethindrone (0.4 mg), and seven tablets containing only ferrous fumarate (75 mg) [53].
Progestin-only pills, which are associated with more breakthrough bleeding (BTB) than combination pills, are
rarely prescribed except in lactating women. In contrast, parenteral forms of progestin-only contraception are
commonly prescribed, particularly in women who cannot take estrogen (table 7). Progestin-only
contraceptives (oral, injectables, implants, and intrauterine devices [IUDs]) are reviewed in detail elsewhere.
(See "Progestin-only pills (POPs) for contraception" and "Depot medroxyprogesterone acetate for
contraception" and "Etonogestrel contraceptive implant" and "Intrauterine contraception: Devices, candidates,
and selection", section on 'LNg-releasing IUDs'.)
Mono- versus multiphasic There are several types of combination pills. Monophasic pills contain the
same dose of estrogen and progestin in each of the 21 hormonally active pills. Attempts to lower the total
dose of steroids have resulted in the formulation of low-dose monophasic pills containing a lower daily dose
of both the estrogen and progestin components. While early OC preparations contained as much as 80 to
100 mcg of ethinyl estradiol, the current pills contain on average 20 to 30 mcg. Pills containing less than 50
mcg of ethinyl estradiol have been referred to as "low-dose" pills.
Other "multiphasic" preparations were introduced in the late 1970s and 1980s in an attempt to further lower
the total steroid dose. An example of a biphasic pill is Ortho 10/11, which contains a fixed dose of 35 mcg of
ethinyl estradiol and an increasing dose of norethindrone: 0.5 mg for 10 days and 1 mg for 11 days. Triphasic
preparations contain varying doses of progestin or estrogen plus progestin across the 21 days. One
multiphasic preparation is an "estrophasic" OC (Estrostep) that contains a fixed dose of norethindrone
acetate (1 mg) and a gradually increasing dose of ethinyl estradiol (20 mcg on cycle days 1 to 5, 30 mcg on
days 6 to 12, and 35 mcg on days 13 to 21) in an effort to minimize estrogen-related side effects [54].
Cyclessa is a triphasic preparation containing 25 mcg of ethinyl estradiol with increasing doses of desogestrel
(100, 125, and 150 mcg days 1 to 7, 8 to 14, and 15 to 21, respectively). While these multiphasic regimens
slightly decrease total steroid content over the month, they have no proven clinical advantage over
monophasic preparations [55].
Cyproterone acetate, a progestin agonist and androgen receptor antagonist, is not available in the United
States but is available in Europe and Canada as a combination OC (Diane) containing ethinyl estradiol and
cyproterone acetate. This preparation is often prescribed for acne or hirsutism (table 1).
Hormone-containing contraceptives are also available as an injection, implant, transdermal patch, and
vaginal ring. (See "Contraceptive counseling and selection" and 'Contraceptive patch and vaginal ring'
below.)
Estrogen component
Type Ethinyl estradiol is the estrogen in nearly all currently used OCs. However, a preparation
containing estradiol valerate is available combined with a new progestin (Natazia [estradiol-dienogest]) [56].
This is the first four-phase OC available; the four phases have varying doses of estradiol valerate (1, 2, or 3
mg) and dienogest (0, 2, or 3 mg). Natazia has 26 pills with hormones and two pills without hormones.
Doses
Standard Standard-dose OCs contain 30 to 35 mcg of ethinyl estradiol, but lower doses are also
available.
Lower doses
20 to 25 mcg Many preparations containing only 20 mcg of ethinyl estradiol are available (table 4). A
25 mcg preparation is also available (Tri-Cyclen Lo) with norgestimate 180 mcg days 1 to 7, 215 mcg
days 8 to 14, and 250 mcg days 15 to 21 [57].
In a meta-analysis of 13 trials, contraceptive efficacy appeared to be similar with OCs containing 20 mcg
ethinyl estradiol when compared with pills with higher doses of estrogen, [58]. Women taking 20 mcg
preparations were more likely to have bleeding disturbances, including amenorrhea, infrequent bleeding,
and irregular, frequent bleeding, or BTB and spotting. However, many of the clinical trials compared OCs
containing different types of progestins. As a result, it is unclear whether the higher frequency of bleeding
is due to the lower estrogen dose or to different progestin types.
10 mcg An even lower dose preparation, Lo Loestrin Fe, containing only 10 mcg of ethinyl estradiol is
now available. It has a 28-day dosing schedule: 24 tablets containing 10 mcg ethinyl estradiol and 1 mg
norethindrone, two tablets containing only 10 mcg ethinyl estradiol, and two tablets containing 75 mg
ferrous fumarate [59].
In a one-year, open-label, unpublished study of over 1000 women ages 18 to 35, the pregnancy rate was
2.92 pregnancies per 100 women-years of use (95% CI 1.94-4.21) [59]. This included women who did
not take the pill correctly. This failure rate is similar to what is typically seen with higher dose pills.
Women with a body mass index (BMI) >35 kg/m2 were not studied, so the contraceptive efficacy of this
pill in severely obese women is unknown.
Perimenopausal women These lower-dose pills are often used for nonsmoking, perimenopausal
women who desire contraception, but who also have irregular or heavy menses and/or hormonally related
symptoms that impair quality of life [60]. These preparations provide more than enough estrogen to relieve
vasomotor flushes (which often begin during the perimenopausal transition). One problem that
perimenopausal women often experience when taking OCs is recurrence of hot flushes and premenstrual
mood disturbances during the seven-day pill-free interval. Some preparations contain 10 mcg of ethinyl
estradiol on five of the seven "placebo" days, which may be helpful for some women. Continuous
administration of the pill is another way to avoid the recurrence of hot flashes. (See 'Continuous pill' below
and "Treatment of menopausal symptoms with hormone therapy", section on 'Use of oral contraceptives
during the menopausal transition'.)
Oral contraception should be avoided altogether in obese perimenopausal women, as the risk of venous
thromboembolism increases with both age and BMI; risk appears to be twice as high as for non-obese
women. (See "Risks and side effects associated with estrogen-progestin contraceptives", section on 'Venous
thromboembolic disease'.)
Progestin component As noted above, most available progestins are derived from testosterone and bind
to both the progesterone and androgen receptors. The first- and second-generation progestins, which are still
commonly used, include norethindrone, norethindrone acetate, levonorgestrel, and ethynodiol diacetate
(table 1). Some of these progestins, most notably levonorgestrel, have androgen properties that cause
adverse metabolic effects such as lowering serum high-density lipoprotein (HDL) cholesterol concentrations.
(See 'Pharmacology' above.)
A group of progestins referred to as "third-generation" progestins (norgestimate, desogestrel, and gestodene)

were eventually developed that, in spite of being 19-nortestosterone derivatives, have structural modifications
that lower their androgenic activity. They include the following (table 2 and table 1).
Norgestimate (eg, Ortho-Cyclen or Tri-Cyclen) and desogestrel (eg, Desogen or Ortho-Cept) appear to be the
least androgenic compounds in this class; these drugs are available in the United States, while gestodene is
not (table 1). Although the new progestins bind to the androgen receptor, the affinity is low, and they have
little effect on serum sex hormone-binding globulin (SHBG) concentrations (which are lowered by androgens
and raised by estrogens) [61,62]. It is important to note that in many studies of the new progestins, the
comparison progestin was levonorgestrel [63], which is the most androgenic of the older progestins.
The contraceptive efficacy of OCs containing the new progestins (so-called third-generation OCs) is similar to
that of the older formulations. In addition, when compared with levonorgestrel-containing pills, the newer OCs
have less of an effect on carbohydrate and lipid metabolism. They are, therefore, a good option for women
who have metabolic complications with an older OC (table 1).
Despite these potential advantages, there have been concerns about the safety of the newer progestins.
Several large epidemiologic studies reported an increased risk of deep venous thrombosis with the use of
these progestins, compared with earlier progestins [64]. A similar increase in risk has been reported with OCs
containing cyproterone acetate, drospirenone, and the contraceptive patch compared with levonorgestrel
[65]. However, this area remains controversial; the third-generation pills continue to be widely used (table 1).
(See "Risks and side effects associated with estrogen-progestin contraceptives", section on 'Venous
thromboembolic disease'.)
Antiandrogenic progestins Progestin preparations have been developed that have mild
antiandrogenic activity. These include a compound derived from testosterone (Dienogest) [66], a
spironolactone analog (drospirenone), and cyproterone acetate, which is available worldwide, but not in the
United States (table 1). Dienogest-containing OCs are available in combination with ethinyl estradiol and
estradiol valerate [56].
Drospirenone is derived from 17 alpha-spironolactone; it has progestogenic, antiandrogenic, and

antimineralocorticoid activity. Monophasic OCs containing either 20 or 30 mcg of ethinyl estradiol with 3 mg of
drospirenone (Yaz and Yasmin) are available. Drospirenone appears to be a very weak antiandrogen; the 3
mg dose is estimated to be equivalent to only 25 mg of spironolactone.
Generic preparations are also available.
There are concerns about an excess risk of venous thromboembolism with preparations containing
drospirenone when compared with those containing levonorgestrel. (See "Risks and side effects associated
with estrogen-progestin contraceptives", section on 'Venous thromboembolic disease'.)
In a two-year trial in 900 women randomly assigned to receive either the 30 mcg ethinyl estradiol/3 mg
drospirenone pill or a 30 mcg/150 mcg desogestrel preparation, contraceptive efficacy was similar, but mean
body weight was lower than baseline with the drospirenone pill, presumably due to its antimineralocorticoid
effect [67].
Drospirenone is also effective for acne and hirsutism [68,69], but there is no evidence that it is more effective
than other OCs for hyperandrogenic symptoms. Although drospirenone is an antiandrogen, it is a very weak
one; 3 mg is equivalent to approximately 25 mg of spironolactone.
The 20 mcg preparation has a four-day pill-free interval as opposed to the standard seven-day interval, and is
approved for the treatment of premenstrual dysphoric disorder (PMDD) (but not for premenstrual syndrome
[PMS], eg, women with milder symptoms). (See "Treatment of premenstrual syndrome and premenstrual
dysphoric disorder", section on 'Oral contraceptives'.)
Although drospirenone has potential potassium-sparing effects (due to its antimineralocorticoid activity),
women taking OCs containing drospirenone are no more likely to develop hyperkalemia than women taking
other OC preparations [70,71]. Current package labeling recommends potassium monitoring in the first
month for women who take additional medications that predispose to hyperkalemia (eg, spironolactone,
nonsteroidal anti-inflammatory drugs) [72]. However, in one study, short-term coadministration of an ethinyl
estradiol-drospirenone OC with indomethacin was associated with the same mean serum potassium and
same low rate of serum potassium values above 5.0 mEq/L as indomethacin alone [71]. As noted, there are
concerns about possible excess risks of venous thromboembolism with drospirenone. (See "Risks and side
effects associated with estrogen-progestin contraceptives", section on 'Venous thromboembolic disease'.)
Shorter pill-free interval Since the original OC was first introduced in 1960, most birth control pill
formulations have had 21 days of hormonally active pills followed by seven days of placebo pills. More
recently, extended-cycle and continuous hormone regimens have gained popularity. (See 'Continuous pill'
below.)
In addition, a number of formulations with 24 days of hormone pills and only four days of placebo pills are
now available. It is hoped that contraceptive failures and side effects will be minimized with this approach
[73]. The shorter the pill-free window, the less likely it is that folliculogenesis will occur. With a standard
seven-day pill-free interval, follicles may develop and secrete enough estradiol to "repair" or stimulate
proliferation of the thin endometrium that is a normal consequence of the progestin in the pill [74]. With a
four-day pill-free interval, folliculogenesis is less likely, and endometrial atrophy becomes more likely (which
can result in more BTB in early cycles).
Skipping the pill-free interval altogether results in a very thin atrophic endometrium; BTB is most common
with the continuous or extendedcycle regimens because of this, as described in the following section.
Continuous pill Continuous or extended-cycle OC regimens (where only active hormone pills are taken,
ie, no placebo pills are used) have been used by clinicians for the treatment of a number of disorders
including:
Endometriosis The strategy with this approach is to induce decidualization and subsequent atrophy of
endometrial tissue. This regimen may be as effective as a gonadotropin-releasing hormone (GnRH)
agonist for pain control. (See "Endometriosis: Treatment of pelvic pain" and "Hormonal contraception for
suppression of menstruation".)
Premenstrual dysphoric disorder To reduce symptoms of PMDD by avoiding hormonal fluctuations.

The effectiveness of this regimen for PMDD has not been studied in clinical trials. (See "Treatment of
premenstrual syndrome and premenstrual dysphoric disorder", section on 'Oral contraceptives'.)
Hyperandrogenism. (See 'Use in hyperandrogenism' above.)
For lifestyle reasons, many women without any underlying disease or disorder prefer to take the pill
continuously to minimize the frequency of menses.
https://www.uptodate.com/contents/overview-of-the-use-of-estrogen-progestin-contraceptives/print?source=search_result&search=anticoncepci 10/29
Other therapies that suppress menstruation are discussed separately. (See "Hormonal contraception for
suppression of menstruation".)
Extended-cycle preparations include seven-day intervals of placebo administration approximately every three
months. One example is Seasonale, which has a 91-day cycle (84 days of active hormone [ethinyl estradiol
30 mcg and levonorgestrel 0.15 mg] and seven days of placebo) [75]. A similar preparation, Seasonique,
contains the same active hormones as Seasonale on days 1 through 84, but days 85 through 91 contain a
small dose of ethinyl estradiol (10 mcg) instead of placebo.
A preparation (Lybrel, 20 mcg ethinyl estradiol with levonorgestrel 0.09 mg) designed to be taken every day
with no placebo phase is also available.
Contraceptive efficacy appears to be the same with extended regimens as with cyclic regimens. BTB, which
is due to the development of a thin, atrophic endometrium with continuous progestin exposure, is a common
problem with continuous regimens in early cycles [76-78], but the frequency decreases over time and
becomes similar to that for cyclic regimens [79-81].
Menstrual cramps and premenstrual symptoms appear to be decreased with continuous, compared with
cyclic, regimens [81].
Thus, women choosing extended-cycle regimens should be aware of potential BTB in early cycles, but they
should be reassured that this decreases over time and does not represent a decrease in contraceptive
efficacy. In addition, the bleeding is not a sign of decreased contraceptive efficacy nor is it associated with an
increased risk of endometrial hyperplasia [82].
The long-term safety of continuous regimens has not been established. However, return of menses and
fertility after stopping OCs appears to be normal [83]. (See 'Return of menses after stopping' above.)
Oral contraceptive with folate Folate supplementation is currently recommended for all women with
reproductive potential to prevent neural tube defects. A combination tablet containing an OC (20 mcg ethinyl
estradiol/3 mg drospirenone) and folic acid (451 mcg levomefolate) is available [84]. (See "Folic acid
supplementation in pregnancy".)
Contraceptive patch and vaginal ring A transdermal contraceptive patch (Xulane) is a newer method for
providing hormonal contraception. Xulane patches deliver 20 mcg of ethinyl estradiol and 150 mcg of
norelgestromin daily. The patch is changed once a week for three weeks, followed by one week that is patch
free. Although the dose of ethinyl estradiol is lower than many OCs, this transdermal preparation is
associated with estrogen exposure approximately 60 percent higher than combination OCs containing ethinyl
estradiol 35 mcg [85] and has resulted in a warning from the US Food and Drug Administration (FDA) with
regard to a possible increased risk of venous thromboembolism. (See "Transdermal contraceptive patch",
section on 'Risk of thrombotic events'.)
A contraceptive ring is also available (NuvaRing, which delivers 15 mcg ethinyl estradiol and 120 mcg of
etonogestrel daily) and is worn intravaginally for three weeks of each four-week cycle. (See "Contraceptive
vaginal ring", section on 'Cardiovascular and thromboembolic events'.)
INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, "The Basics"
and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th
grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easy-to-
read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more
detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want
in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail
these topics to your patients. (You can also locate patient education articles on a variety of subjects by
searching on "patient info" and the keyword(s) of interest.)
Basics topics (see "Patient education: Hormonal birth control (The Basics)" and "Patient education:
Choosing birth control (The Basics)")
Beyond the Basics topics (see "Patient education: Long-acting methods of birth control (Beyond the
Basics)" and "Patient education: Hormonal methods of birth control (Beyond the Basics)" and "Patient
education: Birth control; which method is right for me? (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS Oral contraceptives (OCs) are a reliable form of contraception
and have noncontraceptive benefits, as well. Furthermore, the decrease in both estrogen and progestin
content in the last decade has led to a reduction in both side effects and cardiovascular complications. (See
"Risks and side effects associated with estrogen-progestin contraceptives".)
While OCs have several mechanisms of action, the most important mechanism for providing
contraception is inhibition of the midcycle luteinizing hormone (LH) surge, so that ovulation does not
occur. Another potential mechanism of contraceptive action is suppression of gonadotropin secretion
during the follicular phase of the cycle, thereby preventing follicular maturation. However, a substantial
number of women develop follicles while taking an OC that contains 20 to 35 mcg of ethinyl estradiol.
Progestin-related mechanisms include effects on the endometrium, rendering it less suitable for
implantation, and alterations in cervical mucus, which becomes less permeable to penetration by sperm.
(See 'Mechanisms of action' above.)
OCs can be started at any time during the cycle. The preferred approach is the quick start method in
which the woman begins taking OCs on the day that she is given the prescription, as long as pregnancy
is reasonably excluded. An alternative is the Sunday start approach where the woman starts the pill on
the first Sunday after her period begins. (See 'Initiation' above.)
There are a number of medical conditions that represent an unacceptable health risk for combined
estrogen-progestin OC use. The World Health Organization (WHO) has published medical eligibility
criteria (tables) for contraceptive use; the Centers for Disease Control (CDC) modified the tables in 2010.
(See 'World Health Organization' above and 'Centers for Disease Control' above.)
Missed pills (particularly if the missed pills are at the beginning of the pill pack) are a common cause of
contraceptive failure. We suggest that back-up contraception be used for seven days after two missed
pills, regardless of dose (Grade 2C). (See 'Effect of missed pills' above.)
The metabolism of OCs is accelerated by any drug that increases liver microsomal enzyme activity such
as many of the anticonvulsant drugs, including phenytoin and phenobarbital. As a result, the
contraceptive efficacy of an OC is likely to be decreased in women taking these drugs. In contrast, the
metabolism of OCs is not affected by antibiotics, with the exception of rifampin. (See 'Drug interactions'
above.)
There are several types of combination pills. Monophasic pills contain the same dose of estrogen and
progestin in each of the hormonally-active pills. Biphasic or triphasic pills have varying doses of hormone
across the cycle (usually the progestin). There are no proven advantages to the multiphasic regimens.
We suggest starting with a monophasic pill (Grade 2C). (See 'Available preparations' above.)
The estrogen component of nearly all OCs is ethinyl estradiol. Standard OCs today contain 30 to 35 mcg
of ethinyl estradiol, but many pills now contain only 20 mcg. Contraceptive efficacy with the 20 mcg pills
is similar to the standard-dose pills, as long as adherence is good. These lower-dose pills are a good
option for perimenopausal women who have menopausal symptoms (hot flashes) because they also
provide contraception and bleeding control. One OC containing only 10 mcg ethinyl estradiol is now
available. (See 'Estrogen component' above and "Treatment of menopausal symptoms with hormone
therapy", section on 'Use of oral contraceptives during the menopausal transition'.)
Most available progestins have both progestogenic and androgenic activity (table 2 and table 1). A
progestin with pure progestational activity would be ideal because the androgenic activity is not needed
for contraception and it increases side effects and metabolic complications. However, more selective
progestins have been developed; some function as androgen receptor antagonists. To date, they have
no proven clinical advantages over traditional progestins, and some have been associated with a
possible higher risk of venous thromboembolism. (See 'Progestin component' above and "Risks and side
effects associated with estrogen-progestin contraceptives", section on 'Type of progestin'.)
Use of UpToDate is subject to the Subscription and License Agreement.
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Topic 7398 Version 37.0
GRAPHICS
Classification of progestins used in combined oral contraceptive pills
First generation
Norethindrone acetate
Ethynodiol diacetate
Lynestrenol
Norethynodrel
Second generation
dl-Norgestrel
Levonorgestrel
Third generation
Desogestrel
Gestodene
Norgestimate
Unclassified
Drospirenone
Cyproterone acetate
Reproduced with permission from: Reust CE, Espinoza SA, Ruplinger J, Swofford S. What is the approach to
intermenstrual bleeding in a woman taking a combined oral contraceptive? Evidence-Based Practice 2012; 15:29.
Copyright 2013 Family Physicians Inquiries Network.
Graphic 87416 Version 1.0
Level of androgenic activity of progestins in contraceptive pills
Level of activity Androgenic brand name(s)
High Norgestrel
Levonorgestrel
Middle Norethindrone
Norethindrone acetate
Low Ethynodiol
Norgestimate
Desogestrel
Drospirenone
Dienogest
Pregnancy rate (percent) during first year of use of contraceptives
Typical use Correct use
Most effective
Intrauterine device
Copper T or Mirena <1 <1
Etonogestrel implant <1 <1
Female sterilization <1 <1
Vasectomy <1 <1
Effective
Depo-Provera (DMPA) injection 6 <1
Contraceptive patch 9 <1
Contraceptive pills
Progestin-only or combination estrogen-progestin 9 <1
Contraceptive vaginal ring 9 <1
Diaphragm 12 6
Least effective
Condom
Male 18 2
Female 21 5
Sponge
Previous births 24 20
No previous births 12 9
Cervical cap (FemCap)
No previous births 14 N/A
Previous births 29 N/A
Fertility awareness-based methods
Cervical mucus or ovulation 24 3
Symptothermal 24 0.4
TwoDay 24 4
Standards days 24 5
Withdrawal 22 4
Spermicides 28 18
No method 85 85
Data refer to number of pregnancies per 100 women during first year of use.
Typical use: Refers to failure rates for women and men whose use is not consistent or always correct.
Correct use: Refers to failure rates for those whose use is consistent and always correct.
N/A: Indicates data are not available.
Data from:
Hatcher RA, Trussell J, Nelson A, et al. Contraceptive Technology, 20th ed, Bridging the Gap Communications,
Decatur 2011.
Trussell J. Contraceptive failure in the United States. Contraception 2011; 83:397.
Selected hormonal contraceptives: Oral contraceptives (birth control pills) and

other delivery methods
US trade name
Progestin (mg)* Estrogen (micrograms)
(manufacturer)
Monophasic combinations
Beyaz 28 (Bayer) Drospirenone (3) Ethinyl estradiol (20)
Gianvi 28 (Teva)
Loryna 28 (Sandoz)
Nikki 28 (Lupin)
Yaz (Bayer)
Aviane 28 (Teva Women's) Levonorgestrel (0.1) Ethinyl estradiol (20)
Falmina 28 (Northstar)
Lessina 28 (Teva Women's)
Lutera 28 (Actavis)
Orsythia 28 (Qualitest)
Sronyx 28 (Actavis)
Gildess Fe 1/20 (Qualitest) Norethindrone acetate (1) Ethinyl estradiol (20)
Junel Fe 1/20 28 (Teva

Women's)
Larin Fe 1/20 (Teva Women's)
Loestrin Fe 1/20 28 (Warner

Chilcott)
Loestrin 24 Fe (Warner Chilcott)
Microgestin Fe 1/20 28 (Actavis)
Tarina Fe 1/20 (Afaxys)
Apri 28 (Teva Women's) Desogestrel (0.15) Ethinyl estradiol (30)
Desogen 28 (Merck)
Emoquette 28 (Qualitest)
Juleber 28 (Northstar)
Ortho-Cept 28 (Janssen)
Reclipsen 28 (Actavis)
Solia 28 (Prasco)
Ocella 28 (Teva Women's) Drospirenone (3) Ethinyl estradiol (30)
Syeda 28 (Sandoz)
Yasmin 28 (Bayer)
Zarah 28 (Watson)
Altavera 28 (Sandoz) Levonorgestrel (0.15) Ethinyl estradiol (30)
Chateal 28 (Afaxys)
Kurvelo 28 (Lupin)
Levora 28 (Actavis)
Marlissa 28 (Glenmark)
Portia 28 (Teva Women's)
Gildess Fe 1.5/30 (Qualitest) Norethindrone acetate (1.5) Ethinyl estradiol (30)
Junel FE 1.5/30 (Teva Women's)


Larin FE 1.5/30 (Northstar)
Loestrin Fe 1.5/30 28 (Teva

Women's)
Microgestin Fe 1.5/30 28
(Actavis)
Junel Fe 1.5/30 28 (Teva

Women's)
Cryselle 28 (Teva Women's) Norgestrel (0.3) Ethinyl estradiol (30)
Elinest 28 (Northstar)
Low-Ogestrel 28 (Actavis)
Kelnor 28 (Teva Women's) Ethynodiol diacetate (1) Ethinyl estradiol (35)
Zovia 1/35E 28 (Actavis)
Balziva 28 (Teva's Women's) Norethindrone (0.4) Ethinyl estradiol (35)
Briellyn 28 (Glenmark)
Femcon Fe 28 chewable (Actavis)
Gildagia 28 (Qualitest)
Ovcon 35 28 (Actavis)
Philith 28 (Northstar)
Vyfemla (Lupin)
Wymza Fe 28 chewable (Warner

Chilcott)
Zenchent Fe 28 chewable
(Watson)
Brevicon 28 (Actavis) Norethindrone (0.5) Ethinyl estradiol (35)
Modicon 28 (Janssen)
Necon 0.5/35 28 (Actavis)
Nortrel 0.5/35 28 (Teva Women's)
Wera (Northstar)
Alyacen 1/35 28 (Glenmark) Norethindrone (1) Ethinyl estradiol (35)
Cyclafem 1/35 (Qualitest)
Dasetta 1/35 28 (Northstar)
Necon 1/35 28 (Actavis)
Norinyl 1+35 28 (Actavis)
Nortrel 1/35 28 (Teva Women's)
Ortho-Novum 1/35 28 (Janssen)
Pirmella 1/35 (Lupin)
Estarylla (Sandoz) Norgestimate (0.25) Ethinyl estradiol (35)
Mono-Linyah (Northstar)
MonoNessa 28 (Actavis)
Ortho-Cyclen 28 (Janssen)
Previfem 28 (Vintage)
Sprintec 28 (Teva Women's)
Cyestra-35 (Paladin) , Diane-35 Cyproterone (2) Ethinyl estradiol (35)

(Bayer) , Novo-
Cyproterone/Ethinyl estradiol
(Novopharm)
NOTE: Cyproterone hormonal
contraceptive products are not
available in US; Canadian trade

names shown
Zovia 1/50E 28 (Actavis) Ethynodiol diacetate (1) Ethinyl estradiol (50)
Ogestrel 0.5/50 28 (Actavis) Norgestrel** (0.5) Ethinyl estradiol (50)
Necon 1/50 28 (Actavis) Norethindrone (1) Mestranol (50)
Norinyl 1+50 28 (Actavis)
Multiphasic combinations
Natazia (Bayer) Dienogest (0,2,3,0) Estradiol valerate (3,2,2,1)
Lo Loestrin Fe (Actavis) Norethindrone acetate (1,0) Ethinyl estradiol (10,10)
Azurette 28 (Actavis) Desogestrel (0.15,0,0) Ethinyl estradiol (20,0,10)
Kariva 28 (Teva Women's)
Kimidess 28 (Qualitest)
Mircette 28 (Teva Women's)
Pimtrea 28 (Northstar)
Viorele 28 (Glenmark)
Estrostep Fe 28 (Actavis) Norethindrone acetate (1,1,1) Ethinyl estradiol (20,30,35)
Tilia Fe 28 (Actavis)
Tri-Legest Fe 28 (Teva Women's)
Ortho Tri-Cyclen Lo 28 (Janssen) Norgestimate (0.18,0.215,0.25) Ethinyl estradiol (25,25,25)
Caziant 28 (Actavis) Desogestrel (0.1,0.125,0.15) Ethinyl estradiol (25,25,25)
Cesia 28 (Prasco)
Cyclessa 28 (Merck)
Velivet (Teva Women's)
Enpresse-28 (Duramed) Levonorgestrel (0.05,0.075,0.125) Ethinyl estradiol (30,40,30)
Levonest 28 (Northstar)
Myzilra 28 (Qualitest)
Trivora 28 (Actavis)
Ortho Tri-Cyclen 28 (Janssen) Norgestimate (0.18,0.215,0.25) Ethinyl estradiol (35,35,35)
Tri-Estarylla (Sandoz)
TriNessa 28 (Actavis)
Tri-Previfem 28 (Qualitest)
Tri-Sprintec 28 (Teva Women's)
Alyacen 7/7/7 28 (Glenmark) Norethindrone (0.5,0.75,1) Ethinyl estradiol (35,35,35)
Cyclafem 7/7/7 28 (Qualitest)
Dasetta 7/7/7 28 (Northstar)
Necon 7/7/7 28 (Actavis)
Nortrel 7/7/7 28 (Teva Women's)
Ortho-Novum 7/7/7 28 (Janssen)
Pirmella 7/7/7 (Lupin)
Aranelle 28 (Teva Women's) Norethindrone (0.5,1,0.5) Ethinyl estradiol (35,35,35)
Leena 28 (Actavis)
Tri-Norinyl 28 (Actavis) Norethindrone (0.5,1,0.5) Ethinyl estradiol (35,35,35)
Extended combinations
Amethia Lo 91 (Actavis), Levonorgestrel (0.1) Ethinyl estradiol (20,10)

Camresse Lo 91 (Teva),
LoSeasonique 91 (Teva)
Quartette 91 (Teva) Levonorgestrel (0.15) Ethinyl estradiol (20,25,30,10)
Amethia 91 (Actavis), Camrese 91 Levonorgestrel (0.15) Ethinyl estradiol (30,10)

(Teva), Daysee 91 (Lupin),
Seasonique 91 (Teva)
Introvale 91, Jolessa 91 (Barr), Levonorgestrel (0.15) Ethinyl estradiol (30)

Quasense 91 (Actavis)
Continuous combinations
Amethyst 28 (Actavis), Ashlyna Levonorgestrel (0.09) Ethinyl estradiol (20)

28 (Glenmark)
Progestin-only
Camila 28 (Teva Women's) Norethindrone (0.35) None
Debiltane (Northstar)
Errin 28 (Teva Women's)
Heather (Glenmark)
Jencycla (Lupin)
Jolivette 28 (Actavis)
Lyza 28 (Afaxys)
Nora-BE 28 (Actavis)
Norlyroc (Ohm Laboratories)
Nor-QD 28 (Actavis)
Ortho Micronor (Janssen)
Other delivery methods
Ortho Evra (Janssen), Xulane Norelgestromin (releases 0.15 Ethinyl estradiol (releases 35
(Mylan) transdermal patch mg/day) mcg/day)
(weekly)
NuvaRing vaginal ring (Organon) Etonogestrel (releases 0.12 mg/day) Ethinyl estradiol (releases 15
mcg/day)
NOTE: Products with same or similar trade names available outside US may contain different active ingredient(s)
or component strengths. Consult local product information before use.
Fe: contains iron.

* Different progestins are not equivalent on a milligram basis.
Ethinyl estradiol and mestranol are not equivalent on a milligram basis; the results of some studies indicate that 30 to
35 mcg of ethinyl estradiol is equivalent to 50 mcg of mestranol.
Also approved for acne.
Also contains 451 mcg of levomefolate calcium per tablet. Beyaz is taken for 24 days followed by 4 days of levomefolate
calcium alone.
Taken as active pills for 24 days and placebo for 4 days.
Also available in a 21-day regimen.
Also available in a 21-day regimen that does not contain iron.
Loestrin 24 Fe is taken as active pills for 24 days followed by 4 days of iron tablets alone.
** The progestin norgestrel contains two isomers; only levonorgestrel is bioactive. The amount of norgestrel in each
tablet is twice the amount of levonorgestrel.
Lo Loestrin Fe is taken as active pills for 26 days (24 days of the combination and 2 days of ethinyl estradiol only)
followed by 2 days of iron tablets alone.
Introvale, Quasense, and Seasonale (Canada) are taken on a 91-day cycle: 84 days of active pills and 7 days of
placebo. LoSeasonique, Quartette, and Seasonique are taken on a 91-day cycle, but instead of placebo, 10 mcg of ethinyl
estradiol is taken for 7 days.
Adapted with special permission from The Medical Letter on Drugs and Therapeutics, September 14, 2015; Vol. 57
(1477):e133-e134. www.medicalletter.org.
Additional data from:
1. US Food & Drug Administration Orange Book: Approved Drugs with Therapeutic Equivalence Equations. Available
at: http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm (Accessed on September 30, 2015).
2. Lexicomp online. Copyright 1978-2017 by Lexicomp, Inc. All rights reserved.

How to start contraception
When to start (if

the provider is Additional Examinations or
Contraceptive
reasonably certain contraception (ie, tests needed before
method
that the woman is back-up) needed initiation*
not pregnant)
Copper-containing IUD Anytime Not needed Bimanual examination and

cervical inspection
Levonorgestrel-releasing Anytime If >7 days after menses Bimanual examination and

IUD started, use back-up cervical inspection
method or abstain for 7
days
Implant Anytime If >5 days after menses None

started, use back-up
days
Injectable Anytime If >7 days after menses None

days
Combined hormonal Anytime If >5 days after menses Blood pressure

contraceptive started, use back-up measurement
days
Progestin-only pill Anytime If >5 days after menses None

days
BMI: body mass index; CDC: Centers for Disease Control and Prevention; IUD: intrauterine device; STD: sexually
transmitted disease.
* Weight (BMI) measurement is not needed to determine medical eligibility for any methods of contraception because all
methods can be used (United States Medical Eligibility Criteria for Contraceptive Use 2010, US MEC 1) or generally can be
used (US MEC 2) among obese women. However, measuring weight and calculating BMI (weight [kg]/height [m 2]) at
baseline might be helpful for monitoring any changes and counseling women who might be concerned about weight
change perceived to be associated with their contraceptive method.
Most women do not require additional STD screening at the time of IUD insertion if they have already been screened
according to Centers for Disease Control and Prevention's (CDC) STD Treatment Guidelines (available at
http://www.cdc.gov/std/treatment). If a woman has not been screened according to guidelines, screening can be
performed at the time of IUD insertion, and insertion should not be delayed. Women with purulent cervicitis or current
chlamydial infection or gonorrhea should not undergo IUD insertion (US MEC 4). Women who have a very high individual
likelihood of STD exposure (eg, those with a currently infected partner) generally should not undergo IUD insertion (US
MEC 3). For these women, IUD insertion should be delayed until appropriate testing and treatment occurs.
Reproduced from: US Selected Practice Recommendations for Contraceptive Use, 2013: Adapted from the World Health
Organization Selected Practice Recommendations for Contraceptive Use, 2 nd ed. MMWR Morb Mortal Wkly Rep 2013;
62:1.
Quick-start (same-day start) approach to initiation of new birth control method:

Pill, patch, ring, DMPA injection, implant
DMPA: depot medroxyprogesterone acetate; LMP: last menstrual period.

* Refer to UpToDate content on early pregnancy and pregnancy termination.
Patient should use a barrier back-up method such as condoms for the first week after starting a new method.
Unprotected sex includes episodes of sex in which a method of contraception was used but may not have been effective
(eg, breakage of condom, multiple skipped pills).
Refer to UpToDate content on emergency contraception.
For women using ulipristal for emergency contraception, progestin-containing contraception (ie, the pill, patch, ring,
injection, and implant) should not be used for 5 days following ulipristal. For women taking levonorgestrel or combined
estrogen-progestin emergency contraception, the new contraceptive method can be started after the emergency
contraception .
If the patient would like the contraceptive implant, some providers prefer to offer a single injection of DMPA today and ask
the patient to return for the implant within 5 days of the first day of her next menstrual period (to avoid the need for implant
removal if the repeat urine pregnancy test is positive).
Modified from: RHEDI/The Center for Reproductive Health Education In Family Medicine, Montefiore Medical Center, New York
City. Available at: http://www.rhedi.org/clinicians.php. Accessed on July 7, 2016.
Excluding pregnancy
The provider can be reasonably certain that the woman is not pregnant if she has no symptoms or signs
of pregnancy and meets any of the following criteria:
1. She has not had intercourse since her last normal menses.
2. She has been correctly and consistently using a reliable method of contraception.
3. She is within the first seven days after normal menses.
4. She is within four weeks postpartum (for nonlactating women).
5. She is within the first seven days post-abortion or miscarriage.
6. She is fully or nearly fully breastfeeding, amenorrhoeic, and less than six months postpartum.
A systematic review of studies evaluating the performance of a pregnancy checklist compared with urine
pregnancy test to rule out pregnancy concluded the negative predictive value of a checklist similar to the one
above was 99 to 100 percent.
Data from:
Tepper NK, Marchbanks PA, Curtis KM. Use of a checklist to rule out pregnancy: A systematic review. Contraception
2013; 87:661.
Curtis KM, Tepper NK, Jatlaoui TC, et al. United States Medical Eligibility Criteria for Contraceptive Use,
2016. MMWR Recomm Rep 2016; 65:1.
Conditions in which a progestin-only contraceptive may be desirable
Migraine headaches
Age over 35 years and smoker or obese
History of thromboembolic disease
Cardiac disease, especially coronary artery disease or heart failure
Cerebrovascular disease
Early postpartum period
Hypertension with vascular disease or older than 35 years of age
Systemic lupus erythematosus with vascular disease, nephritis, or antiphospholipid antibodies
Hypertriglyceridemia
Adapted from: the American College of Obstetricians and Gynecologists. The use of hormonal contraception in women
with coexisting medical conditions. ACOG practice bulletin #73, 2006.
Contributor Disclosures
Kathryn A Martin, MD Nothing to disclose Robert L Barbieri, MD Nothing to disclose William F Crowley,
Jr, MD Consultant/Advisory Boards: Juniper Pharmaceuticals [Endocrinology (Vaginal progesterone)]; Quest
Diagnostics [Reproductive endocrinology]. Other Financial Interest: Stock ownership: Juniper
Pharmaceuticals [Endocrinology (Transvaginal ring delivery systems)]. Kathryn A Martin, MD Nothing to
disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must conform
to UpToDate standards of evidence.
Conflict of interest policy

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2/11/2017 Overview of the use of estrogen-progestin contraceptives - UpToDate

Official reprint from UpToDate

Overview of the use of estrogen-progestin contraceptives

Authors: Kathryn A Martin, MD, Robert L Barbieri, MD

Another mechanism of contraceptive action is suppression of ovarian folliculogenesis (via suppression of

Alterations in cervical mucus, which becomes less permeable to penetration by sperm.

Impairment of normal tubal motility and peristalsis.

Among the beneficial effects of an OC in women with hyperandrogenism are:

Inhibition of gonadotropin secretion and thereby a decrease in ovarian androgen secretion

Age 35 years and smoking 15 cigarettes per day

Hypertension (systolic 160 mmHg or diastolic 100 mmHg)

Known thrombogenic mutations

Known ischemic heart disease

Systemic lupus erythematosus (positive or unknown antiphospholipid antibodies)

Migraine with aura at any age

Hepatocellular adenoma or malignant hepatoma

NONCONTRACEPTIVE BENEFITS In addition to high contraceptive efficacy, estrogen-progestin

Menstrual cycle disorders

Menorrhagia (see "Hormonal contraception for suppression of menstruation")

Dysmenorrhea (see "Treatment of primary dysmenorrhea in adult women", section on 'Hormonal

Prevention of menstrual migraine (continuous pill) (see "Estrogen-associated migraine", section on

Acne (see "Hormonal therapy for women with acne vulgaris")

Hirsutism (see "Treatment of hirsutism")

Cancer risk reduction

Decreased risk of colon cancer

A group of progestins referred to as "third-generation" progestins (norgestimate, desogestrel, and gestodene)

Drospirenone is derived from 17 alpha-spironolactone; it has progestogenic, antiandrogenic, and

Generic preparations are also available.

Premenstrual dysphoric disorder To reduce symptoms of PMDD by avoiding hormonal fluctuations.

Hyperandrogenism. (See 'Use in hyperandrogenism' above.)

searching on "patient info" and the keyword(s) of interest.)

Use of UpToDate is subject to the Subscription and License Agreement.

85. Devineni D, Skee D, Vaccaro N, et al. Pharmacokinetics and pharmacodynamics of a transdermal

Topic 7398 Version 37.0

Classification of progestins used in combined oral contraceptive pills

Graphic 87416 Version 1.0

Level of androgenic activity of progestins in contraceptive pills

Level of activity Androgenic brand name(s)

Graphic 78782 Version 5.0

Pregnancy rate (percent) during first year of use of contraceptives

Typical use Correct use

Copper T or Mirena <1 <1

Etonogestrel implant <1 <1

Female sterilization <1 <1

Vasectomy <1 <1

Depo-Provera (DMPA) injection 6 <1

Contraceptive patch 9 <1

Progestin-only or combination estrogen-progestin 9 <1

Contraceptive vaginal ring 9 <1

Cervical cap (FemCap)

No previous births 14 N/A

Previous births 29 N/A

Fertility awareness-based methods

Cervical mucus or ovulation 24 3

Graphic 70218 Version 13.0

Selected hormonal contraceptives: Oral contraceptives (birth control pills) and

Beyaz 28 (Bayer) Drospirenone (3) Ethinyl estradiol (20)

Aviane 28 (Teva Women's) Levonorgestrel (0.1) Ethinyl estradiol (20)

Lessina 28 (Teva Women's)

Gildess Fe 1/20 (Qualitest) Norethindrone acetate (1) Ethinyl estradiol (20)

Junel Fe 1/20 28 (Teva

Larin Fe 1/20 (Teva Women's)

Loestrin Fe 1/20 28 (Warner

Loestrin 24 Fe (Warner Chilcott)