SIMILARITIES AND DISSIMILARITIES OF PROGESTINS DR RASHMI INTRODUCTION
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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 FAMILY ESTRANE FAMILY – 1 ST GEN NORTHINDEONE NORETHINDEONE ACETATE ETHYNODIOL DIACETATE GONANE FAMILY – 2 ND GEN LEVONORGESTROL GONANE FAMILY – 3 RD GEN DESOGESTROL NORGESTIMATE SPIRONOLACTONE DERIVATIVE – 4 TH GEN DROSPERINONE
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; 8 th Edition; Philadelphia: Lippincott Williams & Wilkins, 2011: 974 -975. 4
PROFILE OF PROGESTINS �PROGESTATIONAL EFFECT- Progestational selectivity is the degree to which progestational effects are maximised androgen effect minimised �ANDROGENIC ACTIVITY- Side effects like acne and hirsutism
�ESTROGENIC ACTIVITY- capacity to counter the oestrogrenic effect of EE �GLUCOCORTICOID ACTIVITY �MINERALOCORTICOID ACTIVITY
Evolution of progestrogens Ideal progestogen: Should have the closest profile to progesterone. 7
The effect of the pill on weight, hirsutism and acne l. Parameters l. LNG+EE l. DSG+EE l. P-Value l. Base Weight (Kg) l 63. 2± 15. 6 l 65. 3± 10. 6 l 0. 576 l. Terminal Weight (Kg) l 65. 8± 15. 6 l 65. 3± 11. 0 l 0. 902 l. Weight Changes (Kg) l 3. 3± 3. 6 l 0. 0± 2. 5 l 0. 000 l. Base number of acne l 4. 3± 7. 0 l 4. 8± 8. 2 l 0. 758 l. Terminal number of acne l 4. 7± 6. 7 l 1. 8± 3. 6 l 0. 011 l. Number of acne changes l 0. 4± 3. 3 l-3. 0± 6. 2 l 0. 001 l. Base hirsutism severity l 2. 5± 4. 3 l 2. 7± 4. 4 l 0. 836 l. Terminal hirsutism severity l 2. 8± 4. 2 l 1. 0± 2. 0 l 0. 012 l. Hirsutism severity changes l 0. 3± 1. 8 l-1. 7± 2. 9 l 0. 000 l. Weight l. Acne l. Hirsutism Sanam and Ziba, Saudi Med J 32: 23 -26, 2011
RELATIVE RISK OF CVS EVENTS IN USERS OF 2 ND GEN COMPARED WITH 3 RD GEN ARTICLE YEAR TYPE OF STUDY/C V EVENTS CV ADJUST EVENT ED OR STUDIES FOR 2 ND GEN USERS ADJUSTED OR FOR 3 RD GEN USERS TRANSNATIO NAL STUDY 1997 CASE CONTRO L 817/182 MI 3. 21 0. 79 WHO STUDY 1997 CASE CONTRO L 1309/368 MI 5. 01 UNABLE TO DETERMI NE
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 STROKE ARTICLE YEAR TYPE OF STUDY/ ADJUSTED OR STROKE FOR 2 ND GEN OCP USERS ADJUSTED OR FOR 3 RD GEN USERS WHO STUDY 1996 CASE CONTROL 2659/697 1. 53 1. 76 TRANSNATIONAL STUDY 1997 CASE CONTROL 995/220 3. 1 2. 6
ISCHAEMIC STROKE ARTICLE YEAR TYPE OF STUDY/ ADJUSTED STROKE OR FOR 2 ND GEN USERS ADJUSTED OR FOR 3 RD GEN USERS WHO 1996 CASE CONTROL 3978/1018 NO DIFFERENCE NO DIFFEREN CE
RELATIVE RISK OF VENOUS THROMBOEMBOLISM IN USERS OF 2 ND GEN COMPARED WITH 3 RD GEN OCP USERS ARTICLE YEAR TYPE OF STUDY/ ADJUSTED THROMBOTIC ED ODD’S EVENTS ODD’S RATIO FOR 3 rd GEN 2 nd GEN USERS WHO STUDY 1995 CASE CONTROL 2994/769 3. 4 9. 4 TRANSNATION AL STUDY 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 DESOGESTREL LIPID 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 EFFECTS �REDUCES 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 progestins Progestin Estrogenic Anti. Andro- Antiandro- Antimineralo genic estrogenic -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 BSP �Older women Younger women �Highly effective No side effects �Safe Easy to get �Good cycle control Non invasive �Well tolerated �Added benefits �No side effects
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