Break Free from the Pack with
NuvaRing
By: Heather Sandbulte
Overview
Generic Name: etonogestrel and ethinyl
estradiol vaginal ring
 New Administration of birth control by a
vaginal ring
 Invented by a company in the
Netherlands, Organon
 FDA approved in 2001
 The efficacy and safety determined for
women ages 15- 65 years old.

General Structure
Vaginal Ring
 Non-biodegradable
 Flexible
 Transparent
 Outer diameter: 54 mm
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Combination Hormonal
Contraceptive
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Active Ingredients:
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Progestrone: etonogestrel
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Ring Contains: 11.7 mg
Molecular Weight = 324.46
Estrogen: ethinyl estradiol
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Ring Contains: 2.7 mg
Molecular Weight = 296.40
NuvaRing Regimen
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Insertion:
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Removal:
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Once a month exactly one-week
after ring removal
woman vaginally inserts the ring
Various positions
Body’s muscles hold ring in place
After 3rd week of ring use
Hook ring and pull out
Ring-Free Week:
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The 4th week
Body is free of vaginal ring
Withdrawal bleeding occurs
Administration
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Absorbed by vaginal mucosa
Etonogestrel:
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Released at a steady 0.120 mg/day
Bioavailability of 100%
Binds: 32% to sex hormone binding globulin and 66%
to albumin
Ethinyl estradiol:
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Released at a steady 0.015 mg/day
Bioavailability of 55.6%
Binds non-specifically to albumin
Average Serum Concentrations
1 week 2 week
Etonogestrel
(pg/mL)
Ethinyl-estradiol
(pg/mL)
3 week
1578
1476
1374
19.1
18.3
17.6
- Max Concentrations reached during week 1
- Concentrations slowly decrease
www.druglib.com
Overall Mechanism of Action
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Combination of an estrogen with a progestin
suppresses the hypothalamic-pituitary system
Keep a steady dose of hormones
Inhibits spikes in hormone concentrations
The Mechanism Of Action of
Ethinyl Estradiol
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Semisynthetic Estrogen
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Binds to estrogen receptor complex
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Enter Nucleus

Activates DNA transcription of gene
for estrogenic cellular responses

Increases hepatic synthesis of sex
hormone binding globulin (32% of
etonogestrel binds) and thyroidbinding globulin

Suppresses release of follicle
stimulating hormone (FSH) from
anterior pituitary
The Mechanism of Action of
Etonogestrel
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Synthetic form of progesterone
Trick the body into thinking ovulation
has already happened
Binds to Progesterone receptors and
activates progesterone receptor
mediated gene expression
Slowing the release of gonadotropin
releasing hormone (GnRH) from the
hypothalmus and blunt the preovulatory hormone surge of Luteinizing
hormone (LH)
Human Reproduction Article
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Clinical Study:
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40 subjects
average age of 28
treatment of two 30 day cycles
Compared NuvaRing to Combined Oral
Contraceptives
Evaluated:
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Follicle stimulating hormone (FSH): stimulate a women to
produce a mature egg
Luteinizing hormone (LH): triggers the ovarian sac to rupture
and egg is released
17beta-oestradiol (E2) and progesterone levels
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Figure A:
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Figure B:
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E2 levels similar to COC but higher at
ring-free/pill-free periods
Figure D:
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NuvarRing had higher LH
concentrations
Levels low enough for efficiency
Figure C:
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NuvaRing had higher FSH
concentrations
Levels low enough for efficiency
Levels same for both groups
Overall
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NuvaRing concentration levels were
either equal or higher than COC
kept fairly low to prevent pregnancy
Complete inhibition & suppression of
ovulation after 3rd week of NuvaRing
use is the same as that on day 21 of
COC
Duijkers
Additional Pregnancy Prevention
Cervical Mucus thickening
 Increased viscosity slows sperm down
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Clinical Trail on Follicular Diameter
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Combined Oral Contraceptive vs. NuvaRing
Results:
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Both had ovarian suppression
Follicle size regress after NuvaRing Insertion
Max size of 11 mm reached on the 2nd day after ring-free period
(smaller than the follicular size needed for pregnancy)
Remain small for remaining weeks of ring use
Relevance:
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Ovulation of small follicle less likely to succeed to a successful
pregnancy than larger follicle
Duijkers
Phase III Clinical Trial
 Large
study of 2, 218 women
 Evaluated whether pregnancy occurred or not
Small amount of pregnancies compared to total
number of women
Treatment
Cycles
Pregnancies
Women Following Overall
Protocol
20,889
23,298
10
21
Hcp.nuvaring.com
Clinical Study on NuvaRing’s
Tolerability and Acceptance
Performed in the Netherlands by
Department of Obstetric and Gynecology
 1145 women began treatment
 806 women completed the study
 Ring was removed by 90% of applicants
during the ring periods
 Questionnaire given to both participants
that completed the study and the ones that
did not
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Questionnaire's Results
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800 completers and 280 discontinuers
completed a questionnaire
(Roumen)
Side Effects
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Most common:
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Vaginal infections, irritations, and secretions
Headache
Changes in weight, nausea, and sexual desires
Major Risk:
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Associated with the circulatory system
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Higher risk for myocardial infarction and thromboembolism
Estrogen increases HDL cholesterol and progestin decreases HDL and
increases LDL levels
May increase risk of breast cancer
Decreases:
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Acne
Ectopic pregnancy
Endometrial and ovarian cancers
Iron deficiency anemia
Ovarian cysts
Drug Interactions
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Decrease NuvaRing’s Effectiveness:
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Drugs that induce cytochrome P450 isozymes
 Cytochrome
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P450 metabolizes NuvaRing in the liver
St. John’s Wart
Antibiotics with NuvaRing
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Problem with oral contraceptive:
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While in the gut, ethinyl estradiol is converted to
inactive metabolic forms
The bacteria in the gut converts the metabolites back
into active forms of estrogen so they can be reabsorb
(killing the bacteria will prevent this step from
occurring and the ethinyl estradiol will be excreted)
Numerous studies performed
Result: Amoxicillin and Doxycycline do not have
any pharmacokinetic interactions with NuvaRing
Reason: It enters the bloodstream without being
metabolized in the gut = no need for bacteria
NuvaRing Commercial
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http://video.google.com/videosearch?hl=e
n&q=NuvaRing%20Commerical&um=1&ie
=UTF-8&sa=N&tab=wv#
Advertisement Analysis
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Who is the ad targeting?
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The commercial effectively:
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Women in their 20s or 30s wanting a hassle-free birth
control method and one that is not old-fashion
Downplays the symptoms
Makes it feel like taking a pill each day
Mentions that it is as effective as the pill
The ad does not mention:
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The “ick factor” of NuvaRing
Due to a lack in routine, it may be more difficult to
remember
What NuvaRing actually does except that it is 99%
effective if taken properly
Advertisement Analysis Cont.
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Is this a drug that should be advertised
directly to consumers?
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It may lower unplanned pregnancies
Should the ad discuss what NuvaRing
does and its potential of lowering
unplanned pregnancies

Over three million of the 6.4 million
pregnancies in the United States each year
are unplanned
Is NuvaRing a Necessity

Is this form of birth control a necessity for
our fast-pace society?
Thank you for listening!
References
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Androgens, Estrogens, and Progestins. 05 April 2009. <http://images.google.com>. Path: estrogen receptor.
“Birth Control Vaginal Ring (NuvaRing).” Planned Parenthood. 2 Nov. 2009. 7 March 2009.
<http://www.plannedparenthood.org/health-topics/birth-control/birth-control-vaginal-ring-nuvaring4241.htm>.
Bosch, Torie. “The Pill Killer.” Slate Magazine. 29 Sept. 2008. 3 March 2009
<http://www.slate.com/id/2201022/>.
Your Hormones and Your Fertility Signals. FertilityFriend. 2004. Tamtris Web Services. 20 April 2009.
<http://www.fertilityfriend.com/HelpCenter/FFBook/ff_hormones_and_signs.html>.
Duijkers, Klipping, et al. “Ovarian Function with the contraceptive vaginal ring or oral contraceptive: a
randomized study.” Human Reproduction 27 Aug. 2004: Human Reproduction 2004. Dinox Medical
Investigations, Groenewoudseweg, The Netherlands. 20 March 2009
<http://humrep.oxfordjournals.org/cgi/content/full/19/11/2668>.
Mahoney, Diana. “Two crossover studies: antibiotics don’t affect NuvaRIng.” Health Care Industry. 2004.
International Medical News Group. 8 April 2009
<http://findarticles.com/p/articles/mi_m0CYD/is_14_39/ai_n6144479/>.
“Nuvaring.” Druglib.com. 2009. 10 March 2009 <http://druglib.com>.
“NuvaRing Commerical.” youtube.com
“Nuvaring Information.” Medications.com. 2007. Skylabs Inc. 10 March 2009
<http://medications.com/drugs/nuvaring>.
NuvaRing.MD. 2008. Schering-Plough Corporation. 15 March 2009 <http://hcp.nuvaring.com>.
Roumen, F.J.M.E., Apter, et al. “Efficacy, tolerability, and acceptability of a noval contraceptive vaginal ring
releasing etonogestrel and ethinyl oestradiol.” Human Reproduction March 2001. Atrium Medisch Centrum,
Department of Obstetrics and Gynecology. The Netherlands. 25 March 2009.
<http://humrep.oxfordjournals.org/cgi/content/full/16/3/469?ijkey=f4948eb594ab734c5d6ab2503e5316f6268
4859a>.