Recent Advances in

Hormonal Contraception

18th EFSS Annual International Conference

December 12th -13th , 2013
Dr. Mohamed El Sherbiny
MD Ob.& Gyn. Senior Consultant
Damietta, Egypt
 Hormonal Contraceptives
The need to seek improved combined
oral contraceptives (COCs) efficacy and
acceptability, with fewer health risks,
has been ongoing since the introduction
of COCs more than 50 years ago
 Hormonal Contraceptives
The need to seek improved combined
oral contraceptives (COCs) efficacy and
acceptability, with fewer health risks,
has been ongoing since the introduction
of COCs more than 50 years ago
 Hormonal Contraceptives

I- Combined Hormonal Contraceptives

II- Progestogen Only Contraceptives

 I-Combined Hormonal
Contraceptives

1- Combined Oral Contraceptives (COCs)

2- Combined Monthly Injectables

3- Combined Vaginal Ring

4-combined Hormonal Patches

1-Combined Oral Contraceptives (COCs)
I-High dose Estrogen (E.Estradiol) ≥ 50 µg
II-Low dose Estrogen (E.Estradiol) < 50 µg
1st G EE± 30ug Norethindrone

EE± 30ug Levonergestrel

2nd G

Norgestimate 250ug

Desogestryl 15ug
3rd G EE± 30ug
Gestodene 75ug
4th G
E.E 20ug &/
E.E 30ug &/ Drospirenone 3mg) Estradiol valerate
& Dienogest,
Drospirenone 3mg 24 days on & 4 days off
1-Combined Oral Contraceptives (COCs)
High dose Estrogen (E.Estradiol) ≥ 50 µg

Low dose Estrogen (E.Estradiol) < 50 µg

1st G Norethindrone

2nd G
Levonergestrel

3rd G

EE 30ug
Desogestryl 15ug Gestodene 75ug Norgestimate 250ug

4th G Yasmin Yaz:E.E 20ug

E.E 30ug &/ Drospirenone 3mg) Qlaira
Drospirenone 24 days on & 4 days off Estradiol valerate
3mg & Dienogest,
 2nd Generation

Nordette & Microcept: EE 30ug + Levonergestrel 150 ug

 3rd Generation
The 3rd generation COCs (containing new
progestins: norgestimate, desogestrel and
gestoden) were designed to minimize androgenic
side effect.
EE 30ug

Desogestryl Gestodene
Gestodene 75ug Norgestimate
15ug 75ug 250ug
 4th Generation
Drospirenone has anti-androgenic and anti-
mineraIocorticoid properties.
It was introduced for 3 indications:
 Contraception
 Premenstrual dysphoric disorder
 Acne.
It was believed to be
associated with a lower
risk of thrombosis.

Yasmin:E.E 30ug &/Drospirenone 3mg

Which is First Choice For Women
Starting COCS?
A monophasic COC containing 30 μg EE

with norethisterone or levonorgestrel is

a suitable first pill .

Faculty of Sexual and Reproductive

Healthcare Clinical Guidance 2012
Which is First Choice For Women
Starting COCS? Why?
 There is no evidence to support the use of
biphasic or triphasic COCs.
 Norethisterone- and levonorgestrel-
containing COCs may have a lower risk of VTE
than COCs containing desogestrel &gestodene.
 Efficacy of 20 and 30 μg EE COCs is similar,

but unscheduled bleeding is more

common with
Faculty of Sexual 20 μg COCs.
and Reproductive Healthcare Clinical
Guidance 2012
Risk of Venous Thrombosis
 The relative risk of VT for COCs with 30-35
μg ethinylestradiol (EE) and gestodene,
desogestrel, cyproterone acetate or
drospirenone were similar and 50-80%
higher than for COCs with levonorgestrel.
 COCs with the lowest dose of EE and good
compliance should be prescribed—that is,
30 μg ethinylestradiol with levonorgestrel
Stigman etal., BMJ 2013;347:f5298 doi: 10.1136 ,Meta-analysis ,Sep 2012
 Short Interval Regimen
Yaz:E.E 20ug & /Drospirenone
3mg). 24 days o n& 4 days interval off

Beyaz:E.E 20ug & /Drospirenone 3mg)

+ 451 mcg levomefolate (folic acid )
24 days on & 4 days interval off
Short Interval Regimen
Yaz is currently the only COC with

reported evidence for and approved

indication in the treatment of emotional and
physical symptoms of premenstrual dysphoric
disorder and has shown improvement in
productivity, social activities, and
relationships Raymond &Andrson ,Medicine Reports Ltd 2010
 Short Interval Regimen
Lowest E2 :Lo Loestrin® Fe

24 blue tablets :1 mg norethindrone acetate &

10 µg ethinyl estradiol
 2 white tablets :10 mcg ethinyl estradiol 24 US
Dollar
 2 brown tablets : 75 mg ferrous fumarate.
 Short Interval Regimen
Lowest E2 :Lo Loestrin® Fe
The failure rate is similar to what is typically
seen with higher dose pills.
Women with a body mass index >35 kg/m2
were not studied, so the contraceptive
efficacy of this pill in severely obese women
is unknown. .Martin & Barbieri , UpToDate ,Novamber, 2013
Multiphasic or Quadriphasic

Optimised to provide:
 Good efficacy (adjusted
pearl index of 0.34) and at
the same time
 Satisfactory cycle control
QLAIRA® .
Oestradiol valerate and Dienogest tablets
 QLAIRA®
Contraceptive tablets
Oestradiol valerate (E2V) and
 Dienogest (DNG) Visanne

For Qlaira®, the registration procedure for the indication

“treatment of heavy menstrual bleeding (HMB) in women
who desire oral contraception” was successfully concluded in
October 2010 in the European Union..
Oestradiol valerate (E2V) : is the first preparation
using natural oestradiol, but clinical benefits over
the older preparations remain to be confirmed .
Dienogest (DNG)
 Quadriphasic COCs (QLAIRA) &
Heavy Menstrual Bleeding
Overall, E2V/DNG was associated with an 88%
reduction in median menstrual blood loss (from

142 mL to 17 mL/cycle) after 6 months of

treatment, compared with a 24% reduction with

placebo (from 154 mL to 117 mL/cycle)

Fraser et al., Eur J Contracept Reprod Health Care 2011;16:258–

269
Which is First Choice For Women
Starting COCS? Is it the Quadriphasic?
Further evidence is needed to determine
whether quadriphasic differ from monophasic
COCs in contraceptive effectiveness, bleeding
pattern, minor side effects and acceptability.
Until then, we recommend monophasic pills
containing 30 μg estrogen as the first choice for
women starting oral contraceptive use.

Huib et al., Cochrane Database Systematic Review, 9 NOV 2011

Combined Vaginal Ring
Nuva Ring
Releases :Etonogestrel 120 µg & EE 15 µg/day
3 weeks in and 1 week out.
Simple (once/M)&Easy to use
2.7 mg

11.7 mg

New: Extended Regimens

7Ws in &one Ws out / 13Ws in &one W out / One year continuous .
Miller et al, 2005 Obstet Gynecol. 5 Sep;106(3):473-82
Extended or Continuous Combined
Hormonal
Contraceptive Regimen
(E/C CHC Regimen)
Extended or Continuous Regimen Strategy

Strategy with this approach is to induce

decidualization and subsequent atrophy of
endometrial tissue.
This regimen may be as effective as a GnRH
agonist for pain control.

Martin &Barbieri UpToDate Novamber 2013

Extended or Continuous Regimen
Indications:
1-Endometriosis
2-Premenstrual dysphoric disorder or tension ( headache

or mood changes )
3-Life style : Personal, religious, and cultural beliefs may
affect women’s attitudes towards bleeding and

menstruation. (III)
4-Menorrhagia or dysmenorrhea
Martin &Barbieri UpToDate November 2 013
Extended or Continuous Regimen
Extended COC pills:12weeks pills+1w no pill 30 ug EE/150 ug
LNG( eg Nordette)
Disadvantage:Breakthrough bleeding or breakthrough
spotting (BTB/BTS)
Andreson& Hait, 2003 Contraception;68:89-96 Multicentric RCT

30 ug EE/3mg Drosperinone (Yasmin)

Extended COC pills:24 weeks pills+1w no pill*
Extended COC pills:52 weeks pills+1w no pill**
For BTB or BTS 3-day hormone-free interval
*Sulak et al, 2006 Am J Obstet Gynec. ;195:935-41. RCT
**Cofee et al, 2007 Contraception.;75:444-9

Nuva Ring
Every (49-day cycle), every91-day, or continuous (364-day)
Miller et al, 2005 Obstet Gynecol. 5 Sep;106(3):473-82
Extended or Continuous Regimen
Dedicated CHC
A few dedicated continuous or extended
combined hormonal contraceptive products
have been studied in a variety of regimens.
Seasonal
84 days :ethinyl estradiol 30 µ &
Levonorgestril 0.15 mg
 7days : placebo
Lybrel : 365 day
90 µ levonorgestrel
20 µ ethinyl estradiol
Lybrel was approved by FDA on May 22, 2007
Extended CHC Versus Cyclic Regimen
They were similar in terms of :
 Contraceptive efficacy (pregnancy rates)
 Safety profiles
 Compliance
 Higher satisfaction with extended
regimens.

SOGC ,Canadian Consensus GuidelineNo. 195, July 2007

Extended or Continuous CHC Regimen
Disadvantages
 Irregular bleeding may last as long as the first
6 months of use especially among women who
have never before used COCs.
If bothersome bleeding : stop taking pills for 3 or 4
days and then start taking it continuously again.
 More supplies needed —15 to 17 packs every
year instead of 13.

SOGC ,Canadian Consensus GuidelineNo. 195, July 2007

Martin &Barbieri UpToDate November 2 013
Extended or Continuous Regimen
Safety
The short-term safety is similar to that of
cyclic regimens. (III)

Long-term safety : currently unavailable.

If there is a greater risk than with long-term
use of cyclic regimens, it is likely to be
minimal. (III)

SOGC ,Canadian Consensus Guideline No. 195, July 2007

Hee et al., Acta Obstetricia et Gynecologica Scandinavica 92 125–136 (2013)

 Progestogen
Only
Contraceptives
Progestogen-only Contraceptives
Depo-subQ provera 104 ®(Pfizer)
It is asubcutaneous preparation of depot medroxy-
progesterone acetate (DMPA) 104 mg in 0.65 mL. ,
It was determined in pharmacokinetic studies to
meet the minimum serum concentration required
to provide consistent ovulation
suppression over 3 the user.
Depo-subQ provera 104 Vs DMPA-IM

Depo-subQ provera 104®(Pfizer)

Similar efficacy, if not better
 It allows self-administration by the user.
Similar bleeding disturbances .
A modest weight gain (of up to 4.5 kg) by
3 years was reported
Levonorgestrel Intrauterine Device LNG-IUD
LNG Intrauterine System LNG-IUS

Mirena®
Contains 52 mg LNG Bayer
Releases 20 ug / day for 5 years
Very effective(<0.1%per year).
Lowest ectopic among contraceptives(0.02%per year)
Continuation rates 80 %
Spotting first 6 months& amenorrhoeas later.
LNG-IUD LNG Intrauterine System LNG-IUS

Skyla ® Bayer
Smallar than
Mirena
For:Nuligravida&
Narrow cervix
Contains 13.5 mg LNG
(Vs 52 mg in Mirena )
Releases14 ug↓to 5ug/day
for 3 years (Vs 20 ug ↓ to
10ug /day 5 years in Mirina

FDA approval Feb. 2013

Ulipristal Acetate Contraceptive
Vaginal Ring (UPA-CVR)
The Population Council UPA CVR is composed
of micronized UPA mixed in a silicone rubber
Matrix releasing 600–800 mcg/day of UPA.
UPA is selective progesterone receptor
Modulators.
It is a novel estrogen-free contraceptives
for ongoing use.
The ring is designed to be worn continuously
for 3 months with intervals of one month.
Jensen , Contraception 87 314–318 (2013)
 Ulipristal Acetate Contraceptive
Vaginal Ring (UPA-CVR)

UPA-CVR delivery system is under development

Jensen , Contraception 87 (2013) 314–318

Progesterone-releasing Vaginal
Ring (Progering)
Progering is a 3-month progesterone-
releasing ring(10 mg /d) for use in
lactating women.
It is not absorbed if present in breast milk.
It prolongs lactational amenorrhea which
is a health benefit for women with anemia
Pregnancy rate :1.5 /100 women/Y and did not
differ significantly from the IUD.
Brache et al. , Contraception 87 (2013) 264–272
 What Are The Options?
Emergency Contraceptive Pill
 Oral Levonorgestrel (LNG)
 CHCs pill “Less longer used”
 Ulipristal acetate (UPA)
(ellaOne®)
Copper IUD Family Planning: A Global Handbook for
FSRH (RCOG ) Guidance 2011 Providers 2011
 Levonorgestrel (LNG)

The WHO-recommended
regimen for emergency
contraception is:
1500 µg LNG as a

single dose.
WHO 2005 Contraplan II
 Ulipristal Acetate (UPA)
The efficacy of UPA has been
demonstrated up to 120 hours and
can be offered to all eligible
women requesting EC during this
time period.
It is the only oral EC licensed for
use between 72 and 120 hours.A
FFPRHC Guidance (RCOG) 2012)
 Ulipristal
Acetate
(UPA)
It is a selective
progesterone receptor
modulators a partial
progesterone
agonist/antagonist
Thank You