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SIMILARITIES AND DISSIMILARITIES OF PROGESTINS. DR.RASHMI. INTRODUCTION. PROGESTINS ARE CHEMICAL DERIVATIVES OF TESTOSTERONE KNOWN AS 19- NORTESTSTERONE DERIVATIVES 8 TYPE OF PROGESTINS AVAILABLE. CLASSIFICATION OF PROGESTINS. Mechanisms of action of PROGESTINS IN COC components. - PowerPoint PPT Presentation
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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…..