.

Hypothalamus/pituitary gland >>>

>>> FSH
>>> LH

>>>

Estrogen ()
Ethinyl estradiol ( )
Mestranol (ethinyl estradiol-3-methyl ether)

MES

Demethylation

EE

Progestin ()
Estrogen

Androgen

Anabolic

0/-

+/0

Estrane; 1st generation

Norethisterone, Lynestrenol, Norethynodrel

+/0

+/0

Gonane; 2nd generation

Norgestrel, Levonorgestrel

0/-

Progestin
17-hydroxyprogesterone (Pregnane; C-21)
Medroxyprogesterone acetate, Megestrol, Cyproterone acetate

19-nortestosterone (C-19)

Gonane; 3rd generation

Desogestrel, Gestodene, Norgestimate,

Norelgestomin

Spironolactone derivative
Drospirenone


(COP)
Monophasic ()
High dose (): EE > 50 mcg
Low dose ( ) : EE 20-35 mcg
Very low dose ( ) : EE <20 mcg
Biphasic ( 2 )
Triphasic ( 3 )
Progestin only pills (POP)
( )


Theoretical or method effectiveness
( )
Classical use effectiveness
(
)
Extended use effectiveness
(
)

Pearl index =

# pregnancy X 1200
Total months of exposure

Life table analysis

Incidence of pregnancy in a specific period of time
Contraceptive options
Non-use
Spermicidal agents
Male condom
Oral contraceptives
Female sterilization

Unintended pregnancy in first one year of use

Typical use
Perfect use
85
85
29
18
15
2
8
0.3
0.5
0.5

Euro J Contr Rep Health Care 2010; 15: 4-16.


Free testosterone ( ) >>>
Free
testosterone

SHBG

Inactive
testosterone

Follicular epidermal hyperproliferation (

)
Increased sebum activity ( )
Presence and activity of Propionibacterium acne ()
Inflammation ()
Harper JC, Semin Cutan Med Surg 2005; 24: 103-6.


Free
testosterone

SHBG

Inactive
testosterone

Estrogen >> increased levels of sex hormone-binding globulin (SHBG)

( SHBG)
Progestin >> blocked androgen receptor , 5-reductase inhibition , less binding
to androgen receptor and SHBG
( , 5-reductase SHBG)
Both >> Suppression of ovarian androgen production
( )
Harper JC, Semin Cutan Med Surg 2005; 24: 103-6.

Maturitas 2003; 46S1: S7-16.

Free testosterone (ng./100 ml.)

2
1.5

1
0.5
0
Pretreatment
Cycle

Cycle 3

Ac Obstet Gynecol Scand Suppl 152:33-39, 1990, p 36.

Cycle 6

Posttreatment
Cycle 2


Tricilest
Yaz
EstroStep FE

Diane
Oilezz

norgestimate 180/215/250 g plus 35-g ethinyl estradiol

drospirenone 3 mg plus ethinyl estradiol 20 g plus a 4-day
hormone-free interval
norethindrone acetate 1 mg plus ethinyl estradiol 20/30/35
g plus a 7-day hormone-free interval or ferrous fumarate
cyproterone acetate 2000 g plus ethinyl estradiol 35 g
desogestrel 25/125 g plus ethinyl estradiol 40/30 g

US FDA
Harper JC, Semin Cutan Med Surg 2005; 24: 103-6.

 In two combined trials, a norgestimate COC showed

reduced total lesion counts (MD-9.32; 95% CI -14.19 to
-4.45), reduced inflammatory lesion and comedones
counts, and more with clinician assessment of improved
acne.
For two combined trials of a drospirenone COC, the
investigators' assessment of clear or almost clear skin
favored the drospirenone group (OR 3.02; 95% CI 1.99 to
4.59). In one trial, the drospirenone-COC group showed
greater percent changes for total lesion count, inflammatory
and non-inflammatory lesion counts, and papule and
closed comedone counts.
A COC with cyproterone acetate showed better acne
outcomes than one with desogestrel, but the studies
produced conflicting results. Likewise, levonorgestrel
showed a slight improvement over desogestrel in acne
outcomes, but results were not consistent.
Few important and consistent differences were found
between COC types in their effectiveness for treating acne.

J Am Acad Dermatol 1997;37:746-54.)

Tricilest

J Am Acad Dermatol 1997;37:746-54.)


% reduction in inflammatory lesion

60
50
40
30
20
10
0

Tricilest

Placebo

*P<.0001 for cycles 2-6. Obstet Gynecol. 1997;89:615-622).

3
4
Cycle

, , ,

IUD
, 1.
, uterine fibroid growth

2 3

IUD
2.

, ,

1-9

1.

2.

,
, ,
, ,
, ,

1.

2.

, 1.

2.
1021
1.

2 3

IUD
2.



(thromboembolism)

WHO 4:

20

focal aura
35

35
15








6

WHO 3: ,

aura 35

35 15
3 6
-6

WHO 2: ,

Sickle cell anemia

35
aura
35
40

(major surgery)

( 30
)
6

WHO 1:

Thalassemia

HIV, malaria, TB

rifampin griseofulvin

(minor
surgery)

New Eng J Med 2012; 366(24): 2257-66.

(EE 0.03/DRSP3.0)

(EE 2.7/ETON 11.7)

(EE 0.75/NRGM 6.0)

30


30

 ..2002

Estrogen

Ethinyl estradiol 750 mcg

20 mcg/day

Progestin

Norelgestromin 6 mg

150 mcg/day

metabolite
norgestimate



7


10




24


7


7 9
2 3 ( 2 3)

7
9
2 3 ( 2 3) 7
( 1)
7

Norgestimate (NGM) + Ethinyl estradiol (EE)

21
NGM 250/
EE 35 mcg

28
NGM 180/ 215/ 250
/ EE 35 mcg

NGMN 6 mg/
EE 600 mcg


: Evra
:
Cilest
Tricilest
: Cilest
: Tricilest