Dienogest+ Ethinyl Estradiol Role in oral contraception & Acne

1. Dienogest+ Ethinyl Estradiol
Role in oral contraception & Acne
DR SHARDA JAIN
Dr Jyoti Agarwal …Caring hearts, healing hands

2. Contents
1
2
3
4
5
Contraception & Hormonal Contraception
Issues with hormonal contraception
Dienogest and Ethinyl Estradiol
Pharmacodynamic profile
Clinical Evidence & Safety
Summary6

3. Introduction
• World’s population has doubled
in size over past 40 years,…….
7.7 billion in 2018……!
• Another 3 billion added over
the next half century

4. Indian population
• In developing countries, rapid population
growth
– Strains essential resources and
– Impedes economic progress.
An increased demand for family planning services
India population- 1.3 billion……….!

5. Need for contraception
• Child-bearing done
• Spacing required between children
• Medical and health reasons
• Financial reasons
• Effective control of reproduction essential for women to achieve
individual goals and sense of well being

6. Contraceptives: A Long Journey
chastity belt
16th century
Sponge, douche and linen condom
18-19th century
Reusable condom in original packing
19th century
Colored condoms
2000
Female condoms
2005
IUCD-19th century
1950-Birth control pill

7. Pearl index
• Pearl index used for measuring the failure rate of
a contraceptive.
• Definition- number of contraception failures per
100 woman years (HWY) of exposure.
• Formula:
Pearl index = (No. of pregnancies x 12) x 100 /
(No. of women in the study x Duration of study in
months)
© Sun Pharmaceutical Industries Limited.
All Rights Reserved.
https://www.mdapp.co/pearl-index-calculator-244/

8. Oral Contraception
• Most oral contraceptives now in widespread use
are combinations of an estrogen and a
progestin.
• At least 100 million women worldwide use
combination oral contraceptives today thus
highlighting their proven safety and efficacy.
• They are highly effective in preventing
pregnancy
Fu H, Darroch JE, Haas T, Ranjit N. Fam Plann Perspect 1999;31:56-63

9. Oral Contraceptive Pills
• Norgestrel
• Medroxyprogesterone
• Norethindrone
• Norgestimate
• Desogestrel
• Gestodene
• Levonorgestrel
• Lynestrenol
• Drospirenone
• Dienogest
1960-1961: 2 to 5 times estrogen and 5 to 10 times progestin
High-dose OCPs linked to increased risks of ischemic stroke, MI, and pulmonary embolism
1970s: rapid reduction of doses to reduce complications w/o reduction in effectiveness
Changes in progestin because effects on glucose and lipids vary according to progestin used
Ethinyl estradiol dosage (20 mcg, 25 mcg, 30 mcg, 35 mcg, or 50 mcg),
First Generation Second Generation Third Generation Fourth Generation
Oral Contraceptive Pills

10. How OCPs work
Estrogen: Ethinyl estradiol Progesterone derivative
↓ FSH ↓ FSH
↓ LH ↓ LH
no follicle develops
no ovulation
maintains endometrial
lining
no breakthrough
bleeding
cervical mucus changes
cervix changes
less sperm
penetration

11. Other Benefits of OCs
 Ovarian cancer
 50% reduction even in patients with f/h of ovarian cancer
 Benefits persist for at least 10-20 y after discontinuation
 Endometrial cancer
 Reduction in risk
 Benefits persist for long time
 Menstrual disorders and Anemia
 Reduction of DUB
 Reduce blood flow and risk of anemia
 Acne or Pimples
 Reduction in acne severity

12. Issues with Oral Contraception

13. Need Gap
Levonorgestrol + Ethinyl estradiol= LNG+EE
Desogestrol +Ethinyl estradiol= DSG+EE
Drosperinone+Ethinyl estradiol= DRSP+EE
Dienogest + Ethinyl estradiol= DNG+EE
What we need? OC Pills Used Disadvantages
LNG+EE, Higher Pearl Index-1.98
DSG+EE, 1.12
DRSP+EE <1
Return of Fertility LNG+EE, DRSP+EE <2
Minimal Side Effects
Thyroid imbalance LNG+EE, DRSP+EE T3 resin uptake levels decrease
Glucose imbalance LNG+EE, DRSP+EE Glucose Tolerance decreased
Lipid Metabolism LNG+EE Deranged Lipid Profile
Androgenic DSG+EE, LNG+EE Side effects like hirsutism, virilism
Acne CPA+EE Inflammatory lesions
High contraceptive
efficacy

14. So we need a COC…..
• Which improves tolerability and acceptability while maintaining
efficacy
• Reduction in the dose of the estrogen component
• Introduction of new progestogens with favorable clinical profiles

15. Introducing…….

16. DIENOGEST + ETHINYL ESTRADIOL
Combination-
1ST TIME IN INDIA….!

17. Classification of Progestogens
Ruan X, et al. Maturitas. 2012; 71: 337–344.

18. Dienogest
• Orally active synthetic
• 4th generation progestin
• Differs from other 19-norprogestogens by
having cyanomethyl group rather than
ethinyl group at 17 position
McCormack PL. Drugs. 2010; 70 (16): 2073-2088.

19. Latest Progestin
Umene K, et al. Oncol Rep. 2013; 29(3): 855-60.

20. 1st-generation
2nd-generation
3rd-generation
4th-generation
Have progesterone (P) action & androgenicity
More potent P action & relatively greater
androgenicity
Even more potent P action & less androgenicity
ADR: acne, hirsutism, obesity, increased libido and
virilism occur due to androgenicity
No androgenicity
Inhibit ovulation, follicle development, growth of
endometrial cells & cytokine production
Progestins- Generations
Umene K, et al. Oncol Rep. 2013; 29(3): 855-60.

21. 4th-generation Progestins
• Dienogest, drospirenone, nestorone*
• Blocks angiogenesis & inhibits neovascularization (Dienogest)
• No ADRs like:
– Decreased BMD
• Antiandrogenic activity
– No androgenic effects such as acne, hirsutism,
obesity, increased libido and virilism
• No steroid hormone action other than progesterone
*Sitruk-Ware R. Drugs Aging. 2004; 21(13): 865-83/ Umene K, et al. Oncol Rep. 2013; 29(3): 855-60.

22. Similarities to
19-nortestosterone derivatives
• Short plasma half-life
(~10h ); no accumulation
Specific properties
of DNG
• No interaction with specific
transport proteins (SHBG, CBG)
• Higher free concentration
(10%) compared with other
Similarities to
progesterone derivatives
• Antiandrogenic activity
• Neutral effect on
cardiovascular & metabolic
systems
• Relatively low inhibition
of gonadotropin secretion
• High oral bioavailability
(> 90%)
• Strong progestational effect on
the endometrium
Dienogest – A “Hybrid” Progestin
Mueck AO. Expert Rev Obstet Gynecol. 2011; 6(1): 5-15.
Combines properties of both
19-nortestosterone & progesterone derivatives
• Direct inhibition of ovarian
estradiol production

23. Pharmacokinetics- Dienogest
Absorption
• Absolute bioavailability of about 96%.
Distribution
• 10% - free form, whilst approx. 90% is bound to albumin
• Short Half-life of dienogest is 9.3 ± 1.8 hours - very little accumulation with
daily administration
Elimination
• Renal to faecal excretion is 3.2.
• Total clearance is 3.66 ± 0.71 L/h after a single dose
Dienogest Ethinylestradiol PI.

24. Pharmacokinetics- Ethinyl Estradiol
Absorption
• Absolute bioavailability is about 44%
• Cmax =1.5 to 4 hours
Distribution
• Highly bound to serum albumin (~98.5 %),
• Induces an increase in serum concentrations of SHBG
Elimination
• 30-50% via the kidneys,
• 30-40% being with the faeces
Dienogest Ethinylestradiol PI.

25. • Central effects
– Inhibition of
gonadotropin
secretion: moderate
suppression of circulating estradiol
• Ovarian function:
anovulation (2 mg
dose)
• Local effects
– Anti-proliferative
– Anti-inflammatory
Hypothalamus
Pituitary gland
Gonadotropins
Estrogen and progesterone
Negative feed-back
Uterus
Ovary
Estrogen
Progesterone
Endometrium
Klipping C, et al. J Clin Pharmacol 2012; 52(11): 1704-13/
Katsuki Y et al. Eur J Endocrinol. 1998; 138: 216–226/
Nakamura M et al. Eur J Pharmacol. 1999; 386: 33–40.
Dienogest: MOA

26. Mechanism of action
E
S
T
R
A
D
I
O
L
P
R
O
G
E
S
T
E
R
O
N
E
“Highly selective” binding to progesterone
receptor
Moderate inhibition of Gn secretion:
↓es endogenous production of estradiol
“Hyperprogestogenic & Hypoestrogenic
environment”
Decidualization & atrophy of ectopic
endometrium

27. DIENOGEST
MOA
Atrophy of ectopic
endometrium
Anti-angiogenic
Anti-inflammatory
Anti-proliferative
Found to normalize NK-cell activity,
no. of cells in peritoneal fluid & IL-
1 production by peritoneal
macrophages
McCormack PL. Drugs. 2010; 70 (16): 2073-2088.

28. Mechanism of action
• Dienogest has weak antigonadotrophic
activity;
• Inhibition of ovulation is thought to occur
mainly via peripheral actions rather than
central effects on the hypothalamus-pituitary
axis resulting in suppression of
gonadotrophin secretion
Drugs 2010; 70 (6): 681-689

29. MOA with Ethinyl Estradiol
• Primary mechanisms are
– Inhibition of ovulation (by suppression of
gonadotrophins)
– Changes in the cervical secretion (blocking the
entry of sperm into the uterus)
Dienogest Ethinylestradiol PI.

30. Indication-DCGI approved
• It is indicated for use as an oral contraceptive
and in the treatment of mild to moderate
acne in women who seek oral contraception.
Each film coated tablet contains
Dienogest………………2mg
Ethinyl Estradiol……..30 mcg

31. Dosage & Administration-21/7
Regimen
• 21/7 regimen
• Once daily
• Withdrawal bleeding: usually starts within 2-3
days following the last tablet and may not
have finished before the next pack is started.
• The patient should begin her next 21 day
regimen after treatment free interval of 7
days.
Dienogest Ethinylestradiol PI.

32. Contraindication
• Presence or risk of venous thromboembolism (VTE)
• Presence or risk of arterial thromboembolism
• Pancreatitis or a history thereof if associated with severe hypertriglyceridemia
• Presence or history of severe hepatic disease as long as liver function values have not returned to
normal
• Use of direct-acting antiviral (DAA) drugs containing ombitasvir, paritaprevir or dasabuvir and
combinations of these.
• Presence or history of liver tumours (benign or malignant)
• Known or suspected sex-steroid influenced malignancies (e.g. of the genital organs or the breasts)
• Undiagnosed vaginal bleeding
• Known or suspected pregnancy
• Hypersensitivity to any of the ingredients
Dienogest Ethinylestradiol PI.

33. Use in special population
• Pregnancy Category B3
• The reproductive toxicity of DNG+EE has not
been assessed in animals.
Dienogest Ethinylestradiol PI.

34. Use in special population
• Use in lactation
• Not be recommended until the nursing mother has completely weaned her child
• Paediatric use
• DNG+EE is only indicated after menarche.
• Use in the elderly
• DNG+EE is not indicated after menopause.
• Patients with hepatic impairment
• Contraindicated in women with severe hepatic diseases whilst liver function values
have not returned to normal.
• Patients with renal impairment
• Not been specifically studied in renally impaired patients
Dienogest Ethinylestradiol PI.

35. Pharmaco Dynamic profile of
Dienogest/Ethinyl Estradiol

36. Thyroid hormones
Drugs 2010; 70 (6): 681-689
Pharmco-
dynamic
profile
Anti-androgenic
Carbohydrate
metabolism
Lipid metabolism
Balanced effect on
hemostasis
IGF1& GH
Adrenal hormones &
BP parameters

37. Anti androgenic properties
• Reduces serum androgen levels.
• Serum levels of SHBG increased significantly,
• Significant decreases in total and free
testosterone levels.
• Antiandrogen activity can be detected after 3–
6 days
• Steady-state levels of androgen parameters
were reached within 3 months
DNG/EE has anti-androgenic activity
Drugs 2010; 70 (6): 681-689

38. Effects on Thyroid hormones
• Free T3 resin uptake is decreased with Levonorgestrol & Drosperinone
• Dienogest/EE: significant increase in serum levels of the transporter
protein thyroxine-binding globulin and total T3
• Levels of free T3 and free T4 did not change significantly, indicating that
the activity of both was unaffected.
• This lack of increased thyroid function activity is due to increases in
thyroxine-binding globulin.
Activity of freeT3 and freeT4 was unaffected with DNG+EE
Drugs 2010; 70 (6): 681-689

39. Effects on carbohydrate Metabolism
• Glucose tolerance may be decreased with Levonorgestrol & Drosperinone
• Dienogest/EE: caused a slight increase in serum insulin levels and insulin resistance
• Small but significant increase in fasting serum levels of insulin and C-peptide,
although values generally remained within the normal range
• No significant increase
– Glucose levels,
– Glycosylated haemoglobin levels or
– Insulin/glucose ratio
No significant increase in glucose levels, glycosylated haemoglobin levels
with DNG+EE
Drugs 2010; 70 (6): 681-689

40. Effects on lipid metabolism
• Predominantly caused by the estrogen component,
• Are similar to those described for other estrogen-predominant low-dose ovulation
inhibitors and are not thought to be deleterious.
A study of 25 volunteers who received six cycles of ethinylestradiol/dienogest 30
mg/2mg showed:
• Nonsignificant increases inHDL cholesterol,
• a significant increase in apolipoprotein A1
• Significant reduction in lipoprotein(a)
These changes were more favourable than for ethinylestradiol combined
with levonorgestrel
Drugs 2010; 70 (6): 681-689

41. Effects on Haemostasis
• Appears to have a balanced effect on the haemostatic system, with
minimal stimulation of both procoagulant and fibrinolytic activities
DNG+EE has balanced effect on haemostatic system
Drugs 2010; 70 (6): 681-689

42. Effects on Adrenal Hormones and
Serum
Blood Pressure Parameters
• Ethinylestradiol/dienogest has only mild
effects on adrenal and serum blood pressure
parameters
DNG+EE has mild effects on adrenal & serum blood pressure parameters
Drugs 2010; 70 (6): 681-689

43. Dienogest
• Unique pharmacokinetic and pharmacological profile, combining some
properties of 19- nortestosterone derivatives with those of progesterone
derivatives.
• In contrast to other nortestosterone derivatives, dienogest has no
– estrogenic,
– antiestrogenic or
– androgenic activity,
• Has strong antiandrogenic properties
Drugs 2010; 70 (6): 681-689

44. Comparison of dienogest with other
progestins
Progestogenic
activity
Anti-
androgenic
activity
Androgenic
activity
Glucocorticoid
activity
Progesterone + + - -
Dienogest + + - -
Drospirenone + + - -
Levonorgestrel + - + -
Norgistimate + - + -
MPA + - - +
NETA + - + -
Desogestrel + - + -
CPA + + - +
Mueck AO. Expert Rev Obstet Gynecol. 2011; 6(1): 5-15.

45. Dienogest + EE fills the Gap
What we need? OC Pills Used Disadvantages Dienogest + EE-Advantage
LNG+EE, Higher Pearl Index-1.98
DSG+EE, 1.12
DRSP+EE <1
Return of Fertility LNG+EE, DRSP+EE <2 No subsequent impairment in fertility
Minimal Side Effects
Thyroid imbalance LNG+EE, DRSP+EE T3 resin uptake levels decrease T3, T4 activity unaffected
Glucose imbalance LNG+EE, DRSP+EE Glucose Tolerance decreased No significant increase in glucose levels
Lipid Metabolism LNG+EE Deranged Lipid Profile More favorable than LNG+EE
Androgenic DSG+EE, LNG+EE Side effects like hirsutism, virilism No androgenic effects
Acne CPA+EE Inflammatory lesions
More Improvement in facial acne as
compared to Crypoterone +EE
High contraceptive
efficacy 0.09

46. CLINICAL EVIDENCE & SAFETY
As an Oral contraceptive

47. Czech Study
single arm
47
n=557(DNG+EE)
21/7 regimen, once
daily for 12 cycles
• Contraceptive
efficacy
• Cycle control
• Dermatological
effects
• Clinical safety
Prospective open –label
multicenter, uncontrolled -
Phase III trial, age-18-35
years healthy women
S.Golbs et al. Exp Clin Pharmacol.2002 Dec;24(10):689-96

48. Contraceptive Efficacy
Three subjects became pregnant
during the trial. The unadjusted
Pearl index was 0.595. The adjusted
Pearl index was 0.198
S.Golbs et al.. Exp Clin Pharmacol.2002 Dec;24(10):689-96

49. Cycle control
• Duration of menstrual bleeding
shortened from 5.3 at baseline
to minimum 4.3 days during
treatment
• Intensity of bleeding reduced
• Frequency of intermenstrual
bleeding fell. At cycle 6 it was
below baseline rate
S.Golbs et al.. Exp Clin Pharmacol.2002 Dec;24(10):689-96
50
10
0
10
20
30
40
50
60
Baseline Cycle 4 onwards
Frequency of dysmenorrhea

50. Dermatological effects-Skin blemishes
18
1
28
1
29
0
0
5
10
15
20
25
30
35
Improved Worsened
cycle 3 cycle 6 cycle 12
S.Golbs et al.. Exp Clin Pharmacol.2002 Dec;24(10):689-96

51. Hair Greasiness
16
2
26
2
32
1
0
5
10
15
20
25
30
35
Improved Worsened
cycle 3 cycle 6 cycle 12
S.Golbs et al.. Exp Clin Pharmacol.2002 Dec;24(10):689-96

52. Acne Vulgaris
15
57
1
18
58
1.8
0
10
20
30
40
50
60
70
Healed Improved Worsened
cycle 6 cycle 12
S.Golbs et al.. Exp Clin Pharmacol.2002 Dec;24(10):689-96

53. SAFETY
• Breast tenderness and headache were the most
frequent of the common complaints due to
treatment with DNG/EE
• The frequency of all complaints decreased steadily
over time
• Only 7.7% of subjects discontinued due to adverse
reactions
• No thrombophlebitis events were noticed
S.Golbs et al. Exp Clin Pharmacol.2002 Dec;24(10):689-96

54. Conclusion
• DNG/EE is a reliable ovulation inhibitor
• It provided good cycle control, reduced the incidence of intermenstrual
bleeding, intensity of menstrual bleeding and frequency of dysmenorrhea
• Due to anti-androgenic properties of the progestogen component DNG,
EE/DNG improved the androgen related conditions such as hair
greasiness,greasy skin disorder and even acne
S.Golbs et al. Exp Clin Pharmacol.2002 Dec;24(10):689-96

55. Poland Study
single arm
n=431(DNG+EE)
21/7 regimen, once
daily for 12 cycles
• Contraceptive
efficacy
• Cycle control
• Dermatological
effects
• Clinical safety
Prospective open –label
multicenter, uncontrolled -
Phase III trial, age-18-35
years healthy women
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

56. Contraceptive efficacy
No women became pregnant during the
clinical trial. The unadjusted
Pearl index was 0
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

57. Cycle Control
• Duration of menstrual
bleeding shortened from 5.4
at baseline to minimum 4 days
during treatment
• Intensity of bleeding reduced
• Frequency of intermenstrual
bleeding fell. At cycle 7 it was
below baseline rate
35
10
0
5
10
15
20
25
30
35
40
Baseline Cycle 3 onwards
Frequency of dysmenorrhea
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

58. Dermatological effects-Skin blemishes
18.8
0.5
27.1
0.3
26.7
0
0
5
10
15
20
25
30
Improved Worsened
cycle 3 cycle 6 cycle 12
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

59. Hair Greasiness
32.6
0.2
49.3
0.3
53.9
0
0
10
20
30
40
50
60
Improved Worsened
cycle 3 cycle 6 cycle 12
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

60. Acne vulgaris
2
80
2
37.1
54.3
0
0
10
20
30
40
50
60
70
80
90
Healed Improved Worsened
cycle 6 cycle 12
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

61. Safety
• Breast tenderness and gastric complaints were the most frequent of
the common complaints
• Frequency of all complaints decreased steadily over time
• Only 5.6% of subjects discontinued due to adverse reactions
• No thrombophlebitis events were noticed
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92

62. CONCLUSION
S.Golbs et al. Methods Find Exp Clin Pharmacol.2002 Nov; 24(9):585-92
• DNG/EE is a reliable ovulation inhibitor
• It provided good cycle control, reduced the incidence of
intermenstrual bleeding, intensity of menstrual bleeding and
frequency of dysmenorrhea
• Due to anti-androgenic properties of the progestogen component
DNG, EE/DNG improved the androgen related conditions such as
hair greasiness,greasy skin disorder and even acne

63. Fertility after discontinuation study
single group
N=652(after
discontinuation of
DNG/EE)
Cumulative
pregnancy rate
within 1 yr
Prospective observational
study ;women who wished to
become pregnant after
discontinuation of DNG/EE
Wiegratz et.al Fertil Steril 2006 Jun;85(6):1812-9

64. Results
• After 1 year of follow-up, the
cumulative pregnancy rate was 86.6%
(full analysis set; n= 706).
• When all participants with complete
data were analyzed (n= 652), the
cumulative pregnancy rate was 94.0%.
• More than 15% of the patients
conceived in each of the first three
cycles after termination of EE/DNG;
• The mean time to pregnancy was 3.5
cycles.
Wiegratz et.al Fertil Steril 2006 Jun;85(6):1812-9

65. Conclusion
• The present prospective study revealed only a slight delay in
regaining fertility during the first three cycles after cessation of
EE/DNG.
• Cumulative rate of conception did not differ from that
observed in fertile women who attempted to become pregnant
without prior contraception.
Wiegratz et.al Fertil Steril 2006 Jun;85(6):1812-9

66. Fertility after Discontinuation of Ethinylestradiol/Dienogest
Drugs 2010; 70 (6): 681-689
About 60% and 56% of women conceived within the first three cycles after
ethinylestradiol dienogest discontinuation . Within
1 year, the cumulative pregnancy rates were 94% and 95%.
A study of fertile women who were trying to become pregnant reported
pregnancy rates of 64% after three menstrual cycles and 91% after 12 cycles.

67. CONCLUSION
• There may be a small delay in conception during the first three cycles
after discontinuation of ethinylestradiol/ dienogest, but there is no
subsequent impairment of fertility
• The duration of use of ethinylestradiol/dienogest did not appear to
influence the rate of conception or the time between discontinuation
and conception
Drugs 2010; 70 (6): 681-689

68. CLINICAL EVIDENCE & SAFETY
In Acne

69. Acne Study - 1
3 groups
69
n=525 (DNG-EE)-21/7 Regimen
n=264 (placebo)
n=537 (CPA/EE)
• Inflammatory
lesion count
• Total lesion count
• Imorovement in
facial acneHealthy women, age 16-45
yrs.; mild to moderate facial
acne investigated over 6
treatment cycles of 28days-
Multinational, multicenter,
three arm, double blind &
randomized trial
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.

70. Results
Variable DNG/EE Placebo Diane-35
% change in
total lesion
count
-54.66 -39.42 -53.56
SD 26.34 33.58 27.49
N 515 259 528
%change in
inflammatory
lesion count
-65.6 -49.47 -64.56
SD 29.89 41.04 31.17
N 511 257 526
Improvement in
facial acne
according to IGA
477
(91.9%)
199
(76.2%)
480
(90.2%)
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.

71. Conclusion
DNG/EE is superior to placebo while similar results for all three variables
were obtained for the DNG/EE and CPA/EE (Diane-35) groups in the
treatment of mild to moderate acne, thus providing a valid option for the
treatment of acne in women seeking oral contraception
E. Palombo-Kinne et al. Contraception 2009 Apr; 79 (4): 282-9Diane-35.

72. Acne Study - 2
single group
72
N=120 (DNG/EE)
Reduction in acne
lesions(duration
=12mnths.
Observational study ; cohort of
females; mild to moderate
acne; age-18-30 yrs.n=120
Cardona JP, et.al. Int J Womens Health 2017 Nov 16;9:835-842

73. Results: Reduction in acne lesions
Cardona JP, et.al. Int J Womens Health 2017 Nov 16;9:835-842
37.8
50
100
40.3
90
100 100
90
94.2
100 100
93.2
0
20
40
60
80
100
120
Comedones Papules Pustules Total lesions
%Reduction
Month 1 Month 6 Month 12
At the end of follow-up, the percentage of reduction of lesions was 94% and 23%
of women had a 100% reduction in acne lesions

74. Results: Reduction in acne lesions
Cardona JP, et.al. Int J Womens Health 2017 Nov 16;9:835-842

75. Conclusion
The continued use of COCPs, ethinylestradiol /dienogest, reduced inflammatory
and non-inflammatory acne lesions in women in childbearing age . For those
who wish to use COCPs, ethinylestradiol μg/dienogest could be a beneficial
alternative.
Cardona JP, et.al. Int J Womens Health 2017 Nov 16;9:835-842

76. SAFETY & TOLERABILITY

77. Safety
Drugs 2010; 70 (6): 681-689

78. Safety
• Changes in body weight were minor
• Incidences decreased throughout the study (0–3.5% at cycle 18).
Good tolerability over 15
years of use.
Drugs 2010; 70 (6): 681-689

79. Safety – Thromophlebitis
In PMS study of ethinylestradiol/dienogest - incidence of superficial
phlebitis/thromboembolic event was 0.05%.
The phase III study reported one case of thrombophlebitis of the leg,
corresponding to a rate of 0.45 events per 1000 women-years.
In the Czech and Polish studies, no thrombophlebitic events occurred.
Incidence rates of venous thromboembolism for desogestrel- and
levonorgestrel-containing oral contraceptives have been estimated at 0.535 and
0.271 per 1000 woman-years, respectively.
Drugs 2010; 70 (6): 681-689

80. To conclude ......
• High bioavailability- 96%
• 90% albumin bound; 10% free
• Short half Life
Unique pharmacokinetic
profile
• Pearl index-DNG/EE-0.09
• No subsequent impairment in fertility
High contraceptive
efficacy
Parameters DNG+EE EE+Levonorgestrel(L
NG)
EE+Desog
estrel
EE+Cyproterone EE+Drosperinone
(DRSP)
Contraceptive
efficacy (Pearl
Index)
0.09 1.98 1.12
-
<1

81. Salient Features
• Reduced intensity & duration of menstrual bleeding
• Improved Dysmenorrhea
Effective cycle control
• Decreased serum androgens
• Lower incidences of Hirsutism
Anti-androgenic
• Levels of free T3 and free T4 did not change significantly
• Minor influence on Lipid & carbohydrate metabolism , adrenal hormones and
blood pressure parameters
• Has a balanced effect on haemostatic system
Pharmacodynamic Profile

82. Salient Features
• Improvement in acne
• Beneficial effect on hair and the skinAnti-Acne
• Well tolerated over almost 15 years of use
• Chance of ADR is low, Mild to moderate in severity
and decrease in incidence over time.
• High patient satisfaction
Safety