Women Health
Suliman Almahmoud PhD.
Estrogens Hormens
Biosynthesis
Metabolism
Steroidal Estrogens:
• Estradiol:
Estradiol is the most potent endogenous estrogen.
exhibitng high anity for the ER and high potency when
administered parenterally.
low oral bioavailability and therapeutc efectveness.
Ethinyl Estradiol and Mestranol
To increase the oral bioavailability of estradiol, we
should prevent metabolic oxidaton of the estradiol C17
hydroxyl group to the corresponding ketone (estrone).
Ethinyl Estradiol is more potent than estradiol, with
doses in the microgram rather than the milligram range
Ethinyl Estradiol is mainly metabolized by method B
They are got Phase II conjugaton (o-glucurindaton, o-
sulfaton, o-methylaton)
Mestranol is a prodrug and, is rapidly metabolized to EE
via O-demethylaton.
Esters of Estradiol
• These estrogen analogues usually are administered
intramuscularly.
• They get slowly hydrolysis
Conjugated Estrogens
• Pregnant mares produce two unique
estrogenic compound
Nonsteroidal Estrogens
• Stllbene are bioisosteres of estrogen
• Structure Actvity relatonship (SAR):
• The aromatc A ring and the C3 hydroxyl group are essental for estrogenic actvity.
• The distance between the C3 and C17 hydroxyl groups, and the presence of planar
hydrophobic also are important. Ideally, the distance between the oxygen atoms of
the C3 and C17 hydroxyl groups should range from 10.3 to 12.1 Å.
• Trans form more actve than cis form.
• Removal of the oxygen functon from positon 3 or 17 or epimerizaton of the 17β-
hydroxyl group of estradiol to the α-conf guraton results in estrogenic analog
Structure Activity relationship (SAR)
of Estrogen:
• Functonality at the C1 positon greatly reduces actvity.
• Only small groups can be accommodated at the 2 and 4
positons.
• Additon of hydroxyl groups at positons 6, 7, and 11 reduces
actvity.
• Removal of the oxygen functon from positon 3 or 17 or
epimerizaton of the 17β-hydroxyl group of estradiol to the α-
confguraton greatly reduces actvity.
• The presence of this unsaturaton substantally in ring B boosts
the estrogenic potency of these estrogens.
• Certain modifcatons at the 17α and 16 positons can lead to
enhanced actvity. F
Estrogen Toxicity:
• Method B of estrogen metabolism can produce O-quinones.
• O-quinones highly electrophile molecule can interact with Nucleophile in our
body.
Estrogen Antagonists:
• Impeded Estrogens: Not Actve estrogen competate with estradiol
Selective Estrogen Receptor
Modulators (SERMs).
Aromatase Inhibitors:
• block the conversion of androgens to
estrogens
• The structure–actvity relatonships for
steroidal aromatase inhibitors indicate that
the best agents are substrate analogs, with
only small structural changes to the A ring and
at C19 permited.
• Analogues that contain aryl functonalites at
the 7α positon have enhanced anity for the
enzyme.
Triazole Derivatives
• They are compettve inhibitors of aromatase and selectvely inhibit
the conversion of testosterone to estrogens
Progestins
Progesterone Metabolism
Structure Activity Relationship(SAR):
• Have some androgenic actvity.
• Removal of the C19 CH3 increase actvity.
• Unsaturaton of ring B or C increase the actvity.
• Removal of the 3-keto functon of norethindrone allows retenton of potent
progestn actvity without androgenic efects.
• Introducton of a halogen or methyl substtuent in the 6α or 7α positons
generally increases actvity.
• substtuents at C17 serve to decrease glucocortcoid acton
• Medroxyprogesterone Acetate:
6α-methyl progesterone analogue
• Megestrol Acetate:
Unsaturaton of ring B
• Norgestmate
Non Androgenic efect
Progestin Antagonists:
