.

Hypothalamus/pituitary gland >>>

>>>
FSH
>>> LH

>>>

Estrogen ()
Ethinyl estradiol ( )

Mestranol (ethinyl estradiol-3-methyl ether)

MES

Demethylation

EE

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

Estroge Androge Anabol

n
n
ic
0

0/-

+/0

Estrane; 1st generation: Norethisterone, Lynestrenol, Norethynodrel

+/0

+/0

Gonane; 2nd generation: Norgestrel, Levonorgestrel

Gonane; 3rd generation: Desogestrel, Gestodene, Norgestimate,

0/-

19-nortestosterone (C-19)

Norelgestomin
Spironolactone derivative
Drospirenone



(COP)

Monophasic (

)
High dose (
): EE > 50 mcg

Low dose ( ) : EE 20-35 mcg

) : EE <20 mcg
Very low dose (

Biphasic (
2 )

Triphasic (
3 )

(Progestin only pills; POP)

(EE
30 mcg)!!!

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


Free testosterone (

) >>>

Free
testostero
ne

SHB
G

Inactive
testosteron
e

Follicular epidermal hyperproliferation (

)
Increased sebum activity (

)
Presence and activity of Propionibacterium acne (

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

Free
testostero
ne

SHB
G

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)
HarperBoth
>> Suppression of ovarian androgen production
JC, Semin Cutan Med Surg 2005; 24: 103-6.

Norgestimate

androgen

/

SHBG

Maturitas 2003; 46S1: S7-16.

Free testosterone (ng./100 ml.)

70%


3

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

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

Yaz

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

EstroStep FE

Diane

cyproterone acetate 2000 g plus ethinyl estradiol 35 g

Oilezz

desogestrel 25/125 g plus ethinyl estradiol 40/30 g

US
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

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
Cycle

, ,
,

IUD

,
, uterine fibroid growth

1.

IUD
2.

, ,

1-9

1.

2.

,

,

, ,

,
,
1.

2.

, 1.

2.

1021 1.

IUD
2.

(thromboembolism)

WHO 4:

20

focal aura
35

35

15

WHO 3: ,

35

aura

35



15
3



6 -6

WHO 2:
,

(major
surgery)

Sickle cell anemia

35

aura

35



( 30

)
40

WHO 1:

Thalassemia

HIV, malaria, TB

rifampin griseofulvin

(minor
surgery)

NORGESTIMAT
E

DESOGESTREL

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)

Norgestimate

Drospirenone

30

10

24

Estroge
n

Ethinyl estradiol
750 mcg

Norelgestro
min 6 mg
metabolite
Progest
in

norgestimate

20 mcg/day
150
mcg/day

7


9

2 3 (
2
3)

9
2 3 (
2 3)

1
30-35 mcg

20-25 mcg

SFDA
U
triphasic norgestimate

biphasic desogestrel

<50 mcg


norgestimate

drospirenone desogestrel

........................