Wednesday, 22 April 2020

Evolution of OCP

 All currently  marketed combination OCs   are composed  of a synthetic estrogen plus  a progestin. The  progestin component   provides  most of the contraceptive  protection  while  the estrogen    provides cycle  control  and boosts the contraceptive effectiveness of the progestin.
All but one of the synthetic progestins currently marketed in the United States in hormonal contraceptives   are derivatives of either  19  nor testosterone or 17 a    acetoxyprogesterne . The derivatives  of  19  nor testosterone    are either estranes or gonanes. The  original   OC  containing   northynodrel an estrane derivative of 19 nor testosterone  is no longer   marketed  but the estrane nor ethindrone and its   derivatives   along with   levonorgestrel and other gonane derivatives are   used in currently   marketed  formulations  .
The goname derivatives   have greater  progestational activity  per unit weight  than estranes  Modification in the chemical structure   of goname  derivatives  resulted  in compounds that have   altered biological    activity. The magnitude of   difference  in androgenic and progestational  effects  produced  by each  progestin   is called selectivity  . the so called third generation progestins  Norgestimate desogestrel and Gestodene derived  from the  gonane  norgestrel have     high selectivity    and demonstrated  high progestational   activity   and low   androgenic  activity   when compared  with the other   gonanes. The  OC  formulations containing desogestrel  nor gestimate and Gestodene are called  third  generation OCs. The  implant   contain etonogestrel  a metabolic of desogestrel.
The  newer  selective progestins  including  DRSP do not counter  the effects  of the estrogen   component  as strongly as the older   progestins and are associated  with higher   sex hormone   binding globulin and other   liver globulins selective progestin. Adjustment   of the new progestin products  with a lower dose  of estrogen is being   studied    and may  result in a better  safety profile.
Only two estrogen    are used in OCPs  in the United  States. The so called first generation OCs   contain   50 ug  of either   EE or menstranol . The second  generation   OCs contain 20-35 ug  of EE  OCs   containing one   of the three newer  gonane   progestins and  are called third generation   OCs .
All the synthetic estrogens   and progestins in OCs have an Ethinyl group at position  C17. The presence of this  Ethinyl group enhances  the oral   activity  of these agents   because they are not as rapidly metabolized as they pass through   the intestinal mucosa   and the liver through   the portal  system EE has   about 100 times   the potency  of an equivalent  weight   of conjugated  equine  estrogen  or estrone   sulfate  for stimulating   synthesis   of hepatic  proteins.
The two  estrogens   used in OCs  , EE and  its 3 methyl  either  menstranol have different  biological potency   . Mestranol must be  demethylated  to EE  to bind to  the estrogen   cytosol  receptor    and become   biologically  active. The degree  of conversion of menstranol to EE varies  among individuals   although overall EE is about 1.7  times as potent   as the same  weight  of mestranol

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