Pharmacology - Female Reproduction and Erectile Dysfunction Flashcards
What are the natural estrogens (3)?
Estradiol (E2) - major circulating estrogen in pre-menopausal women
Estrone (E1) - major circulating estrogen in post-menopausal women
Estriol (E3)
All are natural, steroidal
What cells are primarily responsible for estradiol production in premenopasusal owomen?
Granulosa cells of the ovary
During pregnancy, large amounts of estriol are produced by the placenta.
What nonsteroidal estrogen increased the incidence of clear cell adenocarcinoma of the vagina and cervix in female offspring of patients receiving it?
DES
Diethylstilbestrol
Where is E2 (estradiol) mainly metabolized to E1 (estrone)?
Liver
But first pass effect is large
Estrogen has a negative feedback effect on:
estrogen
FSH
Estrogen has a positive feedback effect on:
FSH and LH, near ovulation
Hormone Replacement Therapy has what deleterious effects?
Risks of: breast cancer stroke MI PE DVT water and salt retention --> BP increases
What other effects can HRT have that are not so harmful?
Increase vagina lubrication Lower LDL, increase HDL increase elasticity of blood vessels/reduce peripheral resistances Decrease bone resorption increase body fat
T/F: Synthetic estrogen, such as Ethinyl estrodiol is frequently used along with Progestin for prevention of pregnancy.
True
Estrogen is also used therapeutically to treat primary hypogonadism (estrogen deficiency) and to reduce bone loss and menopause symptoms in older women
What are the adverse (side) effects of estrogen?
Breast tenderness nausea HTN weight gain headache vaginal bleeding
less common: breast cancer (long term use) cervical and endometrial cancer risk 2x-3x increase risk of DVT, PE stroke, MI, gall bladder disease
What are the major contraindications for estrogen therapy?
Strongly contraindicated in patients with breast or endometrial cancer, endometriosis and undiagnosed vaginal bleeding.
Generally contraindicated in patients with pregnancy, thromboembolic disease, hypertension, hepatic disease or with family history of breast or uterine cancer.
Tamoxifen citrate and clomiphene citrate are both what kind of drug?
Anti-estrogen compounds
competitive antagonists of estrogen receptors
**can also be partial agonist–depends on the target tissue
Why is tamoxifen indicated for estrogen-receptor positive breast cancer and not endometrial cancer?
Because tamoxifen is an estrogen receptor antagonists in breast tissue, but an estrogen receptor agonist in bone and uterine endometrium.
T/F: Estrogen has much higher binding affinity for its receptor than that of Tamoxifen (about 100-1,000 times higher). Therefore, Tamoxifen must be used in a concentration much higher than estrogen to maintain inhibition of breast cancer cells.
True
Prolonged use of Tamoxifen for breast cancer increases endometrial cancer risk.
Are Tamoxifen and Clomiphene both non-steroidal?
Yes
What is the MOA of Clomiphene citrate?
Induces ovulation
It has two isomers, cis-chlomiphene (zuclomiphene) and trans-chlomiphene (enclomiphene)
Blocks estrogen binding to its receptors in the hypothalamus and inhibits estradiolʼs negative feedback on the gonadotropins → increases in the secretion of gonadotropins and LH → leads to ovulation.
