Estrogens Flashcards
What effect does progesterone have on the female body that differentiates it from estrogen?
maintenance of pregnancy
What physiologic effects do estrogen and progesterone share?
development/maintenance of female reproductive tissue, CNS effects
Describe the feedback loop for estrogens and progesterone.
The hypothalamus releases GnRH, which travels to the anterior pituitary. It releases FSH and LH, which travel to the ovaries. They release estrogens and progesterone, which can have a positive or negative effect on feedback.
What happens to the corpus luteum and estrogen/progesterone if pregnancy does not occur?
The corpus luteum degenerates. Estrogen and progesterone levels fall, ending the negative feedback on FSH and LH, so their levels start to rise again near the end of the luteal phase.
Androstenedione is converted to estrone by _________. Then, the most potent estrogen, _________, is synthesized in the ovaries from estrone.
aromatase, 17-beta estradiol
How are estrogens metabolized and excreted?
metabolized in the liver, excreted in the bile (some enters via enterohepatic circulation)
What is one major barrier to delivery of orally administered estrogens?
they undergo extensive hepatic and peripheral effects, can be bypassed with formulations that avoid these effects
What are the metabolic and CV effects of estrogens?
(1) decreased bone resorption
(2) increased coagulability of blood
(3) increased HDL/decreased LDL
(4) stimulation of synthesis of transcortin and SHBG
What are some clinical uses of estrogens?
(1) hormonal contraception
(2) relief of menopause sx (hot flashes, psychological sx, urogenital atrophy/vaginal dryness)
(3) post-menopausal osteoporosis
(4) hormone replacement in primary hypogonadism due to chromosomal disorders or failure of ovarian development
What adverse effects are associated with estrogen use?
(1) postmenopausal uterine bleeding
(2) endometrial carcinoma
(3) breast cancer
(4) nausea
(5) HA
(6) fluid retention/weight gain
Which adverse effects of estrogen therapy can be reduced with cyclic administration and concomitant use of a progestin?
postmenopausal uterine bleeding and endometrial carcinoma
What is one common modification made to estrogens to make them orally active?
alkylation at C17 – prevents hepatic first pass effect
What effect does esterification have on estrogen absorption/dissolution?
It will slow dissolution and, thus, absorption. The net effect is a longer duration of action.
Which structural element of a non-steroidal estrogen is responsible for blocking helix-12 of the estrogen receptor and enhancing activity?
amine side-chain substitution
Which structural elements are crucial for SERM activity?
two hydroxyl groups properly spaced, rigid core to properly space aromatic rings
