DR.RASHMI

INTRODUCTIONPROGESTINS ARE CHEMICAL

DERIVATIVES OF TESTOSTERONE KNOWN AS 19- NORTESTSTERONE DERIVATIVES

8 TYPE OF PROGESTINS AVAILABLE

CLASSIFICATION OF PROGESTINSFAMILY

ESTRANE FAMILY – 1ST GEN NORTHINDEONENORETHINDEONE ACETATEETHYNODIOL DIACETATE

GONANE FAMILY – 2ND GEN LEVONORGESTROLNORGESTROL

GONANE FAMILY – 3RD GEN DESOGESTROLNORGESTIMATE

SPIRONOLACTONE DERIVATIVE – 4TH GEN

DROSPERINONE

4

Mechanisms of action of PROGESTINS IN COC components

Mechanisms of action of COC components

Progestin

Mechanism Result

Suppresses release of LH from anterior pituitary

Inhibits ovulation

Thickens cervical mucus Impervious to sperm penetration

Endometrial effect:

a decidualized bed with exhausted and atrophied glands

Not receptive to Embryo implantation

Speroff L. Oral contraception. In: Clinical Gynecologic Endocrinology and Infertility; 8th Edition; Philadelphia:Lippincott Williams & Wilkins, 2011:974-975.

PROFILE OF PROGESTINSPROGESTATIONAL EFFECT- Progestational

selectivity is the degree to which progestational effects are maximised and androgen effect minimised

ANDROGENIC ACTIVITY- Side effects like acne and hirsutism

ESTROGENIC ACTIVITY- capacity to counter the oestrogrenic effect of EE

GLUCOCORTICOID ACTIVITYMINERALOCORTICOID ACTIVITY

7

Ideal progestogen:Should have the

closest profile to progesterone.

Evolution of progestrogens

The effect of the pill on weight, hirsutism and acne

Sanam and Ziba, Saudi Med J 32:23-26, 2011

0.0121.0±2.02.8±4.2Terminal hirsutism severity

0.000-1.7±2.90.3±1.8Hirsutism severity changes

0.8362.7±4.42.5±4.3Base hirsutism severity

Hirsutism

0.001-3.0±6.20.4±3.3Number of acne changes

0.0111.8±3.64.7±6.7Terminal number of acne

0.7584.8±8.24.3±7.0Base number of acne

Acne

0.0000.0±2.53.3±3.6Weight Changes (Kg)

0.90265.3±11.065.8±15.6Terminal Weight (Kg)

0.57665.3±10.663.2±15.6Base Weight (Kg)

Weight

P-ValueDSG+EELNG+EEParameters

RELATIVE RISK OF CVS EVENTS IN USERS OF 2ND GEN COMPARED WITH 3RD GEN

ARTICLE YEAR

TYPE OF STUDY

STUDY/CV EVENTS

CV EVENT STUDIES

ADJUSTED OR FOR 2ND GEN USERS

ADJUSTED OR FOR3RD GENUSERS

TRANSNATIONAL STUDY

1997 CASE CONTROL

817/182 MI 3.21 0.79

WHO STUDY

1997 CASE CONTROL

1309/368 MI 5.01 UNABLE TO DETERMINE

OCP LIPID AND CARBOHYDRATE PROFILE

OLDER OCP’S

-DECREASE HDL

-INCREASE LDL

-ABNORMAL GTT

-DECREASE SEX HORMONE BINDING GLOBULIN- INCREASE INCIDENCE OF DIABETES

NEWER OCP’S

- INCREASE HDL

- DECREASE LDL

- DOESN’T AFFECT GTT

HEMORRHAGIC STROKEARTICLE YEA

RTYPE OF STUDY

STUDY/STROKE

ADJUSTED OR FOR 2ND GEN OCP USERS

ADJUSTED OR FOR 3RD

GEN USERS

WHO STUDY 1996 CASE CONTROL

2659/697

1.53 1.76

TRANSNATIONAL STUDY

1997 CASE CONTROL

995/220 2.6 3.1

ISCHAEMIC STROKEARTICLE YEAR TYPE OF

STUDYSTUDY/STROKE

ADJUSTED OR FOR 2ND GEN USERS

ADJUSTED OR FOR 3RD GEN USERS

WHO 1996 CASE CONTROL

3978/1018

NO DIFFERENCE

NO DIFFERENCE

RELATIVE RISK OF VENOUS THROMBOEMBOLISM IN USERS OF 2ND GEN COMPARED WITH 3RD GEN OCP USERS

ARTICLE YEAR

TYPE OF STUDY

STUDY/ THROMBOTIC EVENTS

ADJUSTED ODD’S RATIO FOR2nd GENUSERS

ADJUSTEDODD’SRATIO FOR3rd GENUSERS

WHO STUDY 1995 CASE CONTROL

2994/769 3.4 9.4

TRANSNATIONALSTUDY

1995 CASE CONTROL

2243/471 3.2 4.8

DROSPIRENONE vs LEVONORGESTREL DRSP – 1 . Similar contraceptive efficacy and good

cycle control. 2 . Has better tolerance. 3 . Fewer prevalence of premenstrual

symptoms. 4 . Better anti-mineralocorticoid activity 5 . Increased risk of venous thromboembolism . 6 . Increases HDL and no significant change in

LDL. 7 . No effect on carbohydrate metabolism . 8 . Increases potassium level .

DROSPRINONE vs DESOGESTRELLIPID AFTER 6 CYCLES

DROSPRINONE DESOGESTREL

SERUM TRIGLYCERIDE

Increases by 3.97% Increases by 4.16%

SERUM HDL-C Increases by 7.52% Increases by 7.09%

SERUM LDL-C Decreases by 5.88% Decreased by 4.22%

NO SIGNIFICANT EFFECT ON CARBOHYDRATE METABOLISM

LONG TERM EFFECTSREDUCES WEIGHT BY 2% .REDUCES ACNE .BETTER CYCLE TOLERANCE .CAUSES NON FATAL VENOUS

THROMBOEMOLISM .

BEING A SPRINOLACTONE DERIVATIVE , IT HAS POTASSIUM SPARING PROPERTIES.

SO ITS CONTRAINDICATED IN PATIENTS WITH HEPATIC AND RENAL FAILURE.

A comparison of various progestinsProgestin Estro-

genic

Anti-

estrogenic

Andro-

genic

Antiandro-genic

Antimineralo

-corticoid

Progesterone - - - + +

Older progestins:

MPA

Norethisterone

Levonorgestrel

-

-

-

-

+

+

+

+

+

-

-

-

-

-

-

Newer progestins:

Desogestrel

Cyproterone acetate

-

-

-

-

-

-

-

+

-

-

Drospirenone - - - + +

KEY RESULTS

COMBINED ORAL CONTRACEPTIVES CONTAINING DESOGESTREL,DROSPRINONE ARE ASSOCIATED WITH A HIGHER RISK OF VENOUS THROMBOEMBOLISMTHAN LEVONORGESTREL CONTRACEPTIVES.

DISCONTINUATION DUE TO SIDE EFFECTS INCLUDING CYCLE DISTURBANCES WERE MORE LIKELY TO OCCUR IN LNG GROUP

Pregnancy and discontinuation rates were similar in third and fourth generation progestin's.

Overall, a similar number of women in both groups reported side effects, except for breast tenderness which was more common in the DRSP group.

There was a trend towards more nausea and vomiting in the DRSP group.

What do women want from contraception?

Survey 2009 of 16-49 year olds BSPOlder women Younger

womenHighly effective No side effects Safe Easy to get Good cycle control Non invasiveWell tolerated Added benefitsNo side effects

THANK YOU….

THANK YOU…..