www. AJOG.
org
The state of hormonal contraception today: benefits
and risks of hormonal contraceptives: combined
estrogen and progestin contraceptives
Lee P. Shulman, MD
O ver the course of the past 50 years,
modifications have been made to
improve the effectiveness, acceptability,
and tolerability of hormonal contracep-
tives. Initially, the doses of the estrogen and
progestin components were lowered and
formulations were developed containing
only progestin. Subsequently, new proges-
tins were developed to decrease andro-
genic side effects, and, more recently, alter-
native delivery systems were introduced to
improve tolerability and continuance, and
convenience of use.1 All combination hor-
monal contraceptives are highly effective
in preventing pregnancy when used prop-
erly; the changes that have been made to
pill regimens and components along the
course of the past 5 decades have been un-
dertaken to improve tolerability and in-
crease the likelihood of consistent and cor-
rect use to improve overall contraceptive
effectiveness and maximize the noncon-
traceptive benefits associated with contra-
ceptive use.
Benefits and risks of combination
hormonal contraceptives
Understanding the benefits and risks of
contraceptive methods and being able to
communicate those to women are criti-
From the Division of Clinical Genetics,
Feinberg School of Medicine Northwestern
University; Department of Medicinal
Chemistry and Pharmacognosy, University
of Illinois at Chicago College of Pharmacy,
Chicago, IL.
Received Feb. 15, 2011; revised June 2, 2011;
accepted June 10, 2011.
Publication of this article was supported by an
educational grant from Bayer Healthcare
Pharmaceuticals.
The author reports no conflict of interest.
Reprints will not be available.
0002-9378/$36.00
© 2011 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2011.06.057
Discussion of effective birth control methods can be a challenging process for clinicians
because the adoption and consistent use of contraception may be influenced by patients’
fears, myths, and misperceptions. Over the years, new progestins have been included in
combination contraceptives or are used alone to provide effective contraception as well as
to decrease androgenic side effects and ameliorate the symptoms of premenstrual dys-
phoric disorder. Alternative delivery systems and regimens have also been introduced to
improve tolerability and continuance and convenience of use. This is a review of estrogen
and progestin combinations and their effects.
Key words: androgenic effects, contraceptive side effects, menstrual cycle control,
venous thromboembolism
cal to improved acceptability and appro- ceptives have been shown to reduce the
priate use of effective birth control. Pro- risk of ovarian epithelial cancer and en-
viding detailed counseling to women at dometrial cancer without increasing the
the outset that addresses the advantages, risk for breast cancer.3 Combination
disadvantages, benefits, and risks of var- hormonal contraceptives generally re-
ious contraceptive methods, invariably duce androgenic symptoms, with several
leads to better outcomes in the future. oral contraceptive regimens having been
Frequently, misconceptions exist with formally approved for the treatment of
regard to the safety of hormonal contra- mild to moderate acne.2 Many women of
ceptives. Clinicians must balance risks childbearing age experience some degree
against the benefits of contraception in of physical and emotional symptoms re-
the context of a particular women’s lated to their impending menses. Some
health history. Unintended pregnancy is of these menstrual-related health issues
usually the result of a lack of contracep- include heavy menstrual bleeding, head-
tive use or failure of the chosen contra- ache, dysmenorrhea and behavioral,
ceptive method. The impact of unin- emotional, and physical symptoms asso-
tended pregnancy can be significant and ciated with premenstrual dysphoric dis-
encompasses health risks as well as ad- order. Combination hormonal contra-
verse social and economic consequences. ceptives have been shown to ameliorate
Health risks usually pertain to absent or or effectively treat these problems. Re-
poor prenatal care and include an in- cently, in women choosing to use oral
creased risk of maternal and neonatal contraceptives for pregnancy preven-
morbidity and mortality. Social and eco- tion, the 20 mcg EE/3 mg drospirenone
nomic consequences include reduced 24/4 regimen was approved by the US
maternal education and employment Food and Drug Administration (FDA)
options, and an increased likelihood of for the treatment of the symptoms of
welfare dependency. As such, unin- premenstrual dysphoric disorder4 and
tended pregnancies place a substantial the multiphasic E2V/DNG regimen was
social, medical and economic burden on approved in Europe for the treatment of
women and society. heavy menstrual bleeding in women.5
In addition to preventing unintended As with any therapeutic agent, there is
pregnancy, hormonal contraceptives invariably an increased risk for side ef-
have been shown to provide numerous fects and adverse events that is concom-
noncontraceptive benefits.2 Oral contra- itant with the benefits accrued by its use.
Supplement to OCTOBER 2011 American Journal of Obstetrics & Gynecology S9
Supplement
FIGURE 1
Percent of women discontinuing a contraceptive based on choice offered
Shulman. Risks and benefits of hormonal contraceptives. Am J Obstet Gynecol 2011.
Clinicians are in the position to weigh
the risks and benefits of hormonal con-
traceptives for each individual patient so
as to empower that woman to decide
which method, if any, to use to prevent
pregnancy. The use of combination oral
contraceptives is associated with an in-
creased risk for thromboembolic events.
In addition, other cardiovascular risks
are increased especially among women
who are smokers, are obese, or have per-
sonal or family histories of cardiovascu-
lar and other disease. However, many
women believe that hormonal contra-
ceptives are associated with great risk to
their health and well-being. Much of this
concern stems from women reading the
lay press, which highlights women who
have experienced considerable morbid-
ity or even death while using such meth-
ods.6 Unfortunately, such reports rarely,
if ever, present information as to the rel-
ative safety of such methods, especially in
comparison to unintended pregnancy,
which is characterized by profoundly
higher rates of overall morbidity and
mortality. Such fears have a powerful
impact on women and all too often lead
women either to choose less effective
methods of contraception or to use no
method at all, thus placing them at a
much higher risk for pregnancy and its
adverse outcomes.
S10 American Journal of Obstetrics & Gynecology Supplement to OCTOBER 2011
Eliciting a woman’s choice for contra-
ception during consultation is critical to
the process of her finding a method of con-
traception that she can successfully incor-
porate into her lifestyle. Although some
women may find the recommendations of
her clinician to be important, it is the pa-
tient who best knows the type of contra-
ceptive regimen that she is likely to use cor-
rectly and gain the maximal contraceptive
and noncontraceptive benefits associate
with her choice of contraception. Indeed, a
study to determine factors associated with
sustained use of contraceptives found that
when the choice of birth control was de-
nied by providing the patient with a popu-
lar method of oral contraception at the
time of the study, about 72% of women
discontinued its use within 12 months,
whereas only 8.9% of those whose pre-
ferred choice was granted eventually dis-
continued the contraceptive (Figure 1).7
Whereas the disparity between those who
continued with their birth control and
those who did not is impressive, the dis-
continuation rate among those denied a
choice is even more remarkable.
Adoption of effective birth control
methods can be a challenging process for
clinicians because of patient barriers—
fears, myths, and misperceptions. These
can include unrealistic expectations, me-
dia scares, and lack of awareness of nu-
www.AJOG.org
merous noncontraceptive benefits. Of-
fering women choices, discussing benefits
and risks, engaging women in birth-con-
trol decision making, and listening to
women about their concerns and needs all
support effective use.
Nondaily, nonoral combination
hormonal contraceptives
Two nonoral, nondaily combination con-
traceptive methods are available, the vagi-
nal ring and a transdermal patch.8,9 These
methods have a number of characteristics
that make them especially attractive to
women: they are highly effective, conve-
nient, and easy to use. Because these meth-
ods require less frequent attention to the
method than other birth control, they are
less likely to be subject to inconsistent use.
In addition, these methods likely have the
noncontraceptive benefits associated with
other hormonal methods while not requir-
ing daily administration.
Vaginal ring
The vaginal ring is a flexible transparent
ring that is inserted like a tampon. It pro-
vides steady and continuous delivery of
low-dose hormone (120 mcg/d of etono-
gestrel and 15 mcg/d of ethinyl estradiol)
over 3 weeks, after which it is removed
for a hormone-free week.8 Lower doses
of estrogen afforded by vaginal adminis-
tration may reduce the effects associated
with higher doses of estrogen, such as
breast tenderness, nausea, and head-
ache.10 The pharmacokinetics of the ring
show that contraceptive levels of etono-
gestrel and ethinyl estradiol are main-
tained to 35 days of use, suggesting that
women can extend use and may experi-
ence lighter or even absent withdrawal
bleeding during the ring-free week.11
Efficacy, cycle control, and acceptabil-
ity were studied in a population of 2322
women using the vaginal ring and fol-
lowed for more than 23,000 cycles.12 Ef-
ficacy, measured by the Pearl Index, was
0.77 in the per-protocol population and
1.18 in the intent-to-treat group. This
study found that the majority of com-
pleters (96%) were very satisfied with the
ring and 90% of them indicated that they
would recommend the ring to others.
Contraceptive acceptability and con-
tinuance of use are influenced by many
www.AJOG.org
factors, key among which is cycle con-
trol. The Dieben et al12 study reported
good cycle control among the ring users.
Almost all women experienced with-
drawal bleeding, which did not generally
occur outside the ring-free week, and,
when it did, it was mainly spotting rather
than bleeding.12 In another study, the
profile of irregular bleeding was more fa-
vorable with the ring than with an oral
levonorgestrel/ethinyl estradiol contra-
ceptive.10 In this study and in clinical ob-
servation, the incidence of irregular
bleeding in the combination oral contra-
ceptive (COC) group was particularly
high during the first cycle.10 This was not
the experience among women using the
ring, although this may be attributed to
the fact that women starting the pill usu-
ally do so on day 1 of the cycle, whereas
the ring users started on day 5.10
Transdermal patch
The transdermal patch contains 6.00 mg
norelgestromin and 0.75 mg ethinyl es-
tradiol and is a highly effective method of
contraception, applied weekly for 3
weeks with a fourth week off.13 An anal-
ysis of pooled data from 3 open-label
studies reported a Pearl Index of 0.88
and a low failure probability of 0.6%
with the patch.14
The patch is also well accepted by
women, and it may offer advantages over
COCs, including convenience and better
continuance of use. Using data pooled
from 3 studies, researchers assessed com-
pliance patterns of the patch compared
with those of an established oral contra-
ceptive.15 For all cycles, adherence to the
weekly dosing schedule of the patch was
significantly better than that of the oral
contraceptive regardless of age of the
women (P ⬍ .001) (Figure 2).15
A pharmacokinetic study showed mean
steady-state concentrations ranged from
0.305–1.53 ng/mL for the progestin com-
ponent and from 11.2-137 pg/mL for the
estrogen component of the patch.13 In a
study that compared the patch with a COC
containing 250 mcg norelgestromin and
35 mcg ethinyl estradiol, the overall expo-
sure to these steroids (area under the
curve) was greater with the patch.13 A
study examining the pharmacokinetic
FIGURE 2
Percent of women adherent to their assigned contraceptive
regimen (transdermal patch or oral contraceptive)
LNG, levonorgestrel.9
Shulman. Risks and benefits of hormonal contraceptives. Am J Obstet Gynecol 2011.
properties of 3 hormonal contraceptive
formulations (a vaginal ring, the transder-
mal patch, and a COC containing 30 mcg
ethinyl estradiol) found that the maximal
blood level of ethinyl estradiol with the
patch was about 60% less than that of the
COC.16,17 A case-controlled study com-
pared the risk of nonfatal venous throm-
boembolism (VTE) in women using the
transdermal patch to that of women using
a COC containing 35 mcg of ethinyl estra-
diol. The study found that the odds ratio
for VTE for transdermal patch users was
0.9, representing no increased risk for VTE
and similar to the risk observed in new us-
ers of the COC comparator.17 Another
study found a 2-fold increased risk for VTE
with the patch.18 Based on this negative in-
formation, the US FDA issued a warning
concerning the possible increased risk of
VTE with patch use. Since then, a third re-
port of a case-controlled study using post-
marketing data found that in women un-
der 40 years of age, there was no increased
risk of VTE with the transdermal patch,
compared with a levonorgestrel-contain-
ing COC.19 The authors concluded that
the risk of idiopathic VTE in users of the
transdermal patch was not different from
that of users of levonorgestrel-containing
COCs in women 39 years of age or
younger.
Supplement to OCTOBER 2011 American Journal of Obstetrics & Gynecology
Supplement
Combination oral contraceptives
The daily COC remains the most com-
monly used nonbarrier method of re-
versible contraception. When properly
used, it is more than 99% effective.20 In
reality, about half of women use COCs
correctly and consistently,21 a study of
use patterns showed that 37% of women
reported that they discontinued their
COC because of side effects.21 Serious
complications, like deep vein thrombo-
sis or pulmonary embolism, are rare, and
aside from a few persistent intolerable
side effects— breast tenderness, spot-
ting—the pill has few absolute contrain-
dications and several noncontraceptive
benefits. Refer to the package insert to
review the complete list of contraindica-
tions and special considerations. Recent
developments in OCs have focused on:
● The development of a pill or pill regi-
men that improves tolerability and ac-
ceptability.
● Lowering doses and altering delivery
patterns of estrogen and progestins.
● The development of new progestins.
Drospirenone-containing COC
Drospirenone is a novel progestin not
derived from 19-nortestosterone but
rather from 17alpha-spirolactone and
has antimineralocorticoid and antian-
S11
Supplement
FIGURE 3
Comparison of risk for venous thromboembolism in 2 prospective trials
comparing oral contraceptives with and without drospirenone
CI, confidence interval; DVT, deep vein thrombosis; EURAS, European Active Surveillance Study; OC, oral contraceptive; PE, pulmonary
embolism; TE, thromboembolism; VTE, venous thromboembolism.18,19
Shulman. Risks and benefits of hormonal contraceptives. Am J Obstet Gynecol 2011.
drogenic activity.22 Combined with ethi-
nyl estradiol, it is an effective oral contra-
ceptive23,24 and has favorable effects in
women who have premenstrual dys-
phoric disorder (PMDD).22 In addition,
its antimineralocorticoid properties have
the potential to lower body weight (through
water weight change and not loss of fat)
and blood pressure.22
Two prospective studies have been un-
dertaken to examine the cardiovascular
effects of the drospirenone-containing
COC— one conducted in Europe25 and
the other in an American population.26
Both studies found that deep vein
thrombosis and pulmonary embolism
occurred with equal frequency in the
ethinyl estradiol/drospirenone COC and
other COC users (Figure 3).25,26 The US
study observed that a clinician can ex-
pect to find one case of thromboembo-
lism among 769 women over the course
of 1 year if they were prescribed the dro-
spirenone-containing COC.26
Two more-recent studies, both using
European populations, have also exam-
ined thrombotic events in users of
COCs.27,28 The Dutch study found an
increased risk of venous thrombosis,
which differed by type of progestin and
dose of estrogen, with all of the COCs.28
S12 American Journal of Obstetrics & Gynecology Supplement to OCTOBER 2011
The Danish study also found an increased
risk, which differed by type of progestin,
that decreased with duration of use and de-
creasing estrogen dose.27 All of the study
results are now included in the prescribing
information for the drospirenone-con-
taining COCs; however, the FDA also
added a statement that the results of the
Dutch and Danish studies do not provide
convincing evidence of an increased risk
for VTE, given the relatively few number of
VTE cases among drospirenone users in
the Dutch study and a likelihood of ascer-
tainment bias in the Danish study.
The rationale for shortening the hor-
mone-free interval in women using
COCs was improvement in ovarian sup-
pression as well as reduction of adverse
symptoms experienced during the hor-
mone-free interval.29-31 An early study
found that by adding 2 days to the COC
regimen, ovarian suppression improved
contraceptive efficacy.32 This was tested
in the extended use of a low-dose 20-mcg
ethinyl estradiol COC, and results showed
that the efficacy of the 24-day low-dose
COC improved efficacy.33
The COCS of the future
Two COCs in development are a 26-day
multiphasic regimen of estradiol valerate
www.AJOG.org
and dienogest and a COC containing 17
beta-estradiol and nomegestrol ace-
tate.34-36 Although the use of estradiol val-
erate may have some advantages over ethi-
nyl estradiol, there are no head-to-head
studies of ethinyl estradiol and estradiol-
containing pills to date. The 26-day multi-
phasic combination of estradiol valerate
and dienogest provides reliable contracep-
tion and, with only 2 days off, may provide
lighter withdrawal bleeding than does a
traditional pill containing ethinyl estradiol
and levonorgestrel.34
The other new pill contains 17 beta-
estradiol and nomegestrol acetate in a
monophasic regimen. A recent pharma-
cologic and pharmacokinetic study indi-
cates good ovulation suppression with
this combination, with mean maximum
follicular diameter decreased from 19.3
mm before treatment to between 6.9 and
8.2 mm during treatment.36 The findings
from this study are consistent with ovu-
lation inhibition produced by oral con-
traceptives containing ethinyl estradiol
and drospirenone.
As the investigation of new com-
pounds continues, it will add to the array
of effective combination hormonal con-
traceptives available to women. The ex-
pansion of contraceptive choice can only
improve the likelihood that a woman
will find a method of contraception that
she will successfully incorporate into her
lifestyle and use consistently and cor-
rectly for as long as she chooses not to be
pregnant. As many hormonal methods
carry similar capabilities to prevent preg-
nancy, it will be the availability of meth-
ods with unique noncontraceptive ben-
efits that will help women find a method
that is right for them. It is important that
research continues to improve tolerabil-
ity and acceptability of contraceptive op-
tions, preserve efficacy, and delineate
noncontraceptive benefits, while lower-
ing hormone exposure and improving
the safety profile. f
REFERENCES
1. Hormonal contraception: recent advances
and controversies. Fertil Steril 2008;90(Suppl):
S103-13.
2. Blumenthal PD, Edelman A. Hormonal con-
traception. Obstet Gynecol 2008;112:670-84.
3. Hannaford PC, Selvaraj S, Elliott AM, Angus
V, Iversen L, Lee AJ. Cancer risk among users
www.AJOG.org
of oral contraceptives: cohort data from the
Royal College of General Practitioner’s oral
contraception study. BMJ 2007;335:651.
4. Rapkin AJ. YAZ in the treatment of premen-
strual dysphoric disorder. J Reprod Med
2008;53(Suppl):729-41.
5. Jensen JT. Evaluation of a new estradiol oral
contraceptive: estradiol valerate and dienogest.
Expert Opin Pharmacother 2010;11:1147-57.
6. Grossman D, Fernandez L, Hopkins K,
Amastae J, Potter JE. Perceptions of the safety
of oral contraceptives among a predominantly
Latina population in Texas. Contraception 2010;
81:254-60.
7. Pariani S, Heer DM, Van Arsdol MD Jr. Does
choice make a difference to contraceptive use?
Evidence from east Java. Stud Fam Plann
1991;22:384-90.
8. NuvaRing [package insert]. Roseland, NJ:
Organon USA Inc; 2008.
9. Ortho Evra [package insert]. Raritan, NJ:
Ortho-McNeil-Janssen Pharmaceuticals, Inc;
2010.
10. Bjarnadottir RI, Tuppurainen M, Killick SR.
Comparison of cycle control with a combined
contraceptive vaginal ring and oral levonorg-
estrel/ethinyl estradiol. Am J Obstet Gynecol
2002;186:389-95.
11. Timmer CJ, Mulders TM. Pharmacokinetics
of etonogestrel and ethinylestradiol released
from a combined contraceptive vaginal ring.
Clin Pharmacokinet 2000;39:233-42.
12. Dieben TO, Roumen FJ, Apter D. Efficacy,
cycle control, and user acceptability of a novel
combined contraceptive vaginal ring. Obstet
Gynecol 2002;100:585-93.
13. Ortho Evra [package insert]. Raritan, NJ:
ORTHO Women’s Health & Urology, Division of
Ortho-McNeil-Janssen Pharmaceuticals, Inc;
2010.
14. Zieman M, Guillebaud J, Weisberg E, Shan-
gold GA, Fisher AC, Creasy GW. Contraceptive
efficacy and cycle control with the Ortho Evra/
Evra transdermal system: the analysis of pooled
data. Fertil Steril 2002;77(Suppl 2):S13-8.
15. Archer DF, Bigrigg A, Smallwood GH,
Shangold GA, Creasy GW, Fisher AC. Assess-
ment of compliance with a weekly contracep-
tive patch (Ortho Evra/Evra) among North
American women. Fertil Steril 2002;77(Suppl 2):
S27-31.
16. van den Heuvel MW, van Bragt AJ,
Alnabawy AK, Kaptein MC. Comparison of ethi-
nylestradiol pharmacokinetics in three hor-
monal contraceptive formulations: the vaginal
ring, the transdermal patch and an oral contra-
ceptive. Contraception 2005;72:168-74.
17. Jick SS, Kaye JA, Russmann S, Jick H. Risk
of nonfatal venous thromboembolism in women
using a contraceptive transdermal patch and
oral contraceptives containing norgestimate
and 35 microg of ethinyl estradiol. Contracep-
tion 2006;73:223-8.
18. Cole JA, Norman H, Doherty M, Walker AM.
Venous thromboembolism, myocardial infarction,
and stroke among transdermal contraceptive
system users. Obstet Gynecol 2007;109(Pt 1):
339-46.
19. Jick SS, Hagberg KW, Hernandez RK, Kaye
JA. Postmarketing study of ORTHO EVRA and
levonorgestrel oral contraceptives containing
hormonal contraceptives with 30 mcg of ethinyl
estradiol in relation to nonfatal venous thrombo-
embolism. Contraception 2010;81:16-21.
20. Hatcher R, Trussell J, Nelson A, Cates W Jr,
Stewart F, Kowal D. Contraceptive technology,
19th ed. New York, NY: Ardent Media Inc; 2008.
21. Rosenberg MJ, Waugh MS. Oral contra-
ceptive discontinuation: a prospective evalua-
tion of frequency and reasons. Am J Obstet
Gynecol 1998;179(Pt 1):577-82.
22. Oelkers W. Drospirenone, a progestogen
with antimineralocorticoid properties: a short
review. Mol Cell Endocrinol 2004;217:255-61.
23. Yasmin [package insert]. Wayne, NJ: Bayer
HealthCare Pharmaceuticals Inc; 2010.
24. Yaz [package insert]. Wayne, NJ: Bayer
HealthCare Pharmaceuticals Inc; 2010.
25. Dinger JC, Heinemann LA, Kuhl-Habich D.
The safety of a drospirenone-containing oral
contraceptive: final results from the European
Active Surveillance Study on oral contracep-
tives based on 142,475 women-years of obser-
vation. Contraception 2007;75:344-54.
26. Seeger JD, Loughlin J, Eng PM, Clifford CR,
Cutone J, Walker AM. Risk of thromboembo-
lism in women taking ethinylestradiol/dro-
spirenone and other oral contraceptives. Ob-
stet Gynecol 2007;110:587-93.
27. Lidegaard O, Lokkegaard E, Svendsen AL,
Agger C. Hormonal contraception and risk of
Supplement to OCTOBER 2011 American Journal of Obstetrics & Gynecology
Supplement
venous thromboembolism: national follow-up
study. BMJ 2009;339:b2890.
28. van Hylckama Vlieg A, Helmerhorst FM,
Vandenbroucke JP, Doggen CJ, Rosendaal
FR. The venous thrombotic risk of oral contra-
ceptives, effects of oestrogen dose and prog-
estogen type: results of the MEGA case-control
study. BMJ 2009;339:b2921.
29. Sullivan H, Furniss H, Spona J, Elstein M.
Effect of 21-day and 24-day oral contraceptive
regimens containing gestodene (60 microg) and
ethinyl estradiol (15 microg) on ovarian activity.
Fertil Steril 1999;72:115-20.
30. Sulak PJ, Scow RD, Preece C, Riggs MW,
Kuehl TJ. Hormone withdrawal symptoms in
oral contraceptive users. Obstet Gynecol 2000;
95:261-6.
31. Mishell DR Jr. Rationale for decreasing the
number of days of the hormone-free interval
with use of low-dose oral contraceptive formu-
lations. Contraception 2005;71:304-5.
32. Spona J, Elstein M, Feichtinger W, et al.
Shorter pill-free interval in combined oral con-
traceptives decreases follicular development.
Contraception 1996;54:71-7.
33. Poindexter A. The emerging use of the 20-
microg oral contraceptive. Fertil Steril 2001;75:
457-65.
34. Ahrendt HJ, Makalova D, Parke S, Mellinger
U, Mansour D. Bleeding pattern and cycle con-
trol with an estradiol-based oral contraceptive:
a seven-cycle, randomized comparative trial of
estradiol valerate/dienogest and ethinyl estra-
diol/levonorgestrel. Contraception 2009;80:
436-44.
35. Endrikat J, Parke S, Trummer D, Schmidt
W, Duijkers I, Klipping C. Ovulation inhibition
with four variations of a four-phasic estradiol
valerate/dienogest combined oral contracep-
tive: results of two prospective, randomized,
open-label studies. Contraception 2008;78:
218-25.
36. Duijkers IJ, Klipping C, Grob P, Korver T.
Effects of a monophasic combined oral contra-
ceptive containing nomegestrol acetate and
17␤-oestradiol on ovarian function in compari-
son to a monophasic combined oral contracep-
tive containing drospirenone and ethinylestra-
diol. Eur J Contracept Reprod Health Care
2010;15:314-25.
S13