SIMILARITIES AND DISSIMILARITIES OF PROGESTINS

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SIMILARITIES AND DISSIMILARITIES OF PROGESTINS

• DR.RASHMI

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INTRODUCTION

• PROGESTINS ARE CHEMICAL DERIVATIVES OF
  TESTOSTERONE KNOWN AS 19- NORTESTSTERONE
  DERIVATIVES
• 8 TYPE OF PROGESTINS AVAILABLE

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CLASSIFICATION OF PROGESTINS
FAMILY
ESTRANE FAMILY 1ST GEN NORTHINDEONE NORETHINDEONE ACETATE ETHYNODIOL DIACETATE
GONANE FAMILY 2ND GEN LEVONORGESTROL NORGESTROL
GONANE FAMILY 3RD GEN DESOGESTROL NORGESTIMATE
SPIRONOLACTONE DERIVATIVE 4TH GEN DROSPERINONE
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Mechanisms of action of PROGESTINS IN COC
components
Mechanisms of action of COC components Mechanisms of action of COC components
Progestin 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 PhiladelphiaLippincott Williams
Wilkins, 2011974-975.
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PROFILE OF PROGESTINS

• PROGESTATIONAL EFFECT- Progestational selectivity
  is the degree to which progestational effects are
  maximised and androgen effect minimised
• ANDROGENIC ACTIVITY- Side effects like acne and
  hirsutism

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• ESTROGENIC ACTIVITY- capacity to counter the
  oestrogrenic effect of EE
• GLUCOCORTICOID ACTIVITY
• MINERALOCORTICOID ACTIVITY

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Evolution of progestrogens
Ideal progestogen
Should have the closest profile to progesterone.
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The effect of the pill on weight, hirsutism and
acne
Sanam and Ziba, Saudi Med J 3223-26, 2011
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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 FOR 3RD GEN USERS
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
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OCP LIPID AND CARBOHYDRATE PROFILE
OLDER OCPS -DECREASE HDL INCREASE LDL ABNORMAL GTT DECREASE SEX HORMONE BINDING GLOBULIN INCREASE INCIDENCE OF DIABETES
NEWER OCPS INCREASE HDL DECREASE LDL DOESNT AFFECT GTT

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HEMORRHAGIC STROKE
ARTICLE YEAR TYPE 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
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ISCHAEMIC STROKE
ARTICLE YEAR TYPE OF STUDY STUDY/STROKE ADJUSTED OR FOR 2ND GEN USERS ADJUSTED OR FOR 3RD GEN USERS
WHO 1996 CASE CONTROL 3978/1018 NO DIFFERENCE NO DIFFERENCE
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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 ODDS RATIO FOR 2nd GEN USERS ADJUSTED ODDS RATIO FOR 3rd GEN USERS
WHO STUDY 1995 CASE CONTROL 2994/769 3.4 9.4
TRANSNATIONAL STUDY 1995 CASE CONTROL 2243/471 3.2 4.8
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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 .

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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
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LONG TERM EFFECTS

• REDUCES WEIGHT BY 2 .
• REDUCES ACNE .
• BETTER CYCLE TOLERANCE .
• CAUSES NON FATAL VENOUS THROMBOEMOLISM .

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• BEING A SPRINOLACTONE DERIVATIVE , IT HAS
  POTASSIUM SPARING PROPERTIES.
• SO ITS CONTRAINDICATED IN PATIENTS WITH HEPATIC
  AND RENAL FAILURE.

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A comparison of various progestins
Progestin Estro- genic Anti- estrogenic Andro- genic Antiandro-genic Antimineralo -corticoid
Progesterone - - -
Older progestins MPA Norethisterone Levonorgestrel - - - - - - - - - -
Newer progestins Desogestrel Cyproterone acetate - - - - - - - - -
Drospirenone - - -
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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

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• 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.

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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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